{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:02:37Z","timestamp":1791846157542,"version":"4.3.4"},"reference-count":294,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T00:00:00Z","timestamp":1763424000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010621","name":"Medical University of Lublin","doi-asserted-by":"publisher","award":["DS640"],"award-info":[{"award-number":["DS640"]}],"id":[{"id":"10.13039\/501100010621","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010438","name":"Poznan University of Medical Sciences","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100010438","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Aberrant activation of innate immunity promotes the development of pulmonary arterial hypertension (PAH); however, the role of pattern recognition by Toll-like receptors (TLRs) within the pulmonary vasculature remains unclear. To consolidate knowledge (as of June 2025) about TLRs and their interactions with viruses in PAH and to identify therapeutic implications. A narrative review of experimental and clinical studies investigating ten TLRs in the context of the pulmonary vascular microenvironment and viral infections. Activation of TLR1\/2, TLR4, TLR5\/6, TLR7\/8, and TLR9 converges on the MyD88\u2013NF-\u03baB\/IL-6 axis, thereby enhancing endothelial-mesenchymal transition, smooth muscle proliferation, oxidative stress, thrombosis, and maladaptive inflammation, ultimately increasing pulmonary vascular resistance. Conversely, TLR3, through TRIF\u2013IFN-I, preserves endothelial integrity and inhibits vascular remodeling; its downregulation correlates with PAH severity, and poly (I:C) restitution has been shown to improve hemodynamics and right ventricular function. HIV-1, EBV, HCV, endogenous retrovirus K, and SARS-CoV-2 infections modulate TLR circuits, either amplifying pro-remodeling cascades or attenuating protective pathways. The \u201cTLR rheostat\u201d is shaped by polymorphisms, ligand biochemistry, compartmentalization, and biomechanical forces. The balance between MyD88-dependent signaling and the TRIF\u2013IFN-I axis determines the trajectory of PAH. Prospective therapeutic strategies may include TLR3 agonists, MyD88\/NF-\u03baB inhibitors, modulation of IL-6, and combination approaches integrating antiviral therapy with targeted immunomodulation in a precision approach.<\/jats:p>","DOI":"10.3390\/ijms262211143","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T12:33:04Z","timestamp":1763469184000},"page":"11143","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Role of Toll-like Receptors and Viral Infections in the Pathogenesis and Progression of Pulmonary Arterial Hypertension\u2014A Narrative Review"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2945-1601","authenticated-orcid":false,"given":"Agnieszka","family":"Stycze\u0144","sequence":"first","affiliation":[{"name":"Department of Cardiology, Medical University of Lublin, Jaczewskiego 8, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martyna","family":"Krysa","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Medical University of Lublin, Jaczewskiego 8, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9530-6659","authenticated-orcid":false,"given":"Paulina","family":"Mertowska","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0451-4741","authenticated-orcid":false,"given":"Ewelina","family":"Grywalska","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8080-2764","authenticated-orcid":false,"given":"Tomasz","family":"Urbanowicz","sequence":"additional","affiliation":[{"name":"Cardiac Surgery and Transplantology Department, Pozna\u0144 University of Medical Sciences, 1\/2 Dluga Street, 61-848 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maciej","family":"Krasi\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, St Mary\u2019s Hospital, Imperial College Healthcare Trust, London W2 1NY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malwina","family":"Grobelna","sequence":"additional","affiliation":[{"name":"Department of Vascular, Endovascular Surgery, Angiology and Phlebology, Poznan University of Medical Science, 1\/2 D\u0142uga Street, 61-848 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weronika","family":"Topy\u0142a-Putowska","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Medical University of Lublin, Jaczewskiego 8, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5622-7330","authenticated-orcid":false,"given":"Mansur","family":"Rahnama-Hezavah","sequence":"additional","affiliation":[{"name":"Chair and Department of Oral Surgery, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha\u0142","family":"Tomaszewski","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Medical University of Lublin, Jaczewskiego 8, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/1750-1172-8-97","article-title":"Pulmonary Arterial Hypertension","volume":"8","author":"Montani","year":"2013","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"104168","DOI":"10.1016\/j.lpm.2023.104168","article-title":"Pulmonary Arterial Hypertension","volume":"52","author":"Boucly","year":"2023","journal-title":"Presse Med."},{"key":"ref_3","unstructured":"Manek, G., and Bhardwaj, A. (2025). Pulmonary Hypertension. StatPearls, StatPearls Publishing."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1161\/CIRCULATIONAHA.116.022362","article-title":"Systemic Consequences of Pulmonary Hypertension and Right-Sided Heart Failure","volume":"141","author":"Rosenkranz","year":"2020","journal-title":"Circulation"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Funk-Hilsdorf, T.C., Behrens, F., Grune, J., and Simmons, S. (2022). Dysregulated Immunity in Pulmonary Hypertension: From Companion to Composer. Front. Physiol., 13.","DOI":"10.3389\/fphys.2022.819145"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ge, Q., Zhang, T., Yu, J., Lu, X., Xiao, S., Zhang, T., Qing, T., Xiao, Z., Zeng, L., and Luo, L. (2024). A New Perspective on Targeting Pulmonary Arterial Hypertension: Programmed Cell Death Pathways (Autophagy, Pyroptosis, Ferroptosis). Biomed. Pharmacother., 181.","DOI":"10.1016\/j.biopha.2024.117706"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"DeVaughn, H., Rich, H.E., Shadid, A., Vaidya, P.K., Doursout, M.-F., and Shivshankar, P. (2024). Complement Immune System in Pulmonary Hypertension-Cooperating Roles of Circadian Rhythmicity in Complement-Mediated Vascular Pathology. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252312823"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Li, X., Li, S., Zhou, Y., Zhang, T., and Sun, L. (2024). Immunotherapy for Pulmonary Arterial Hypertension: From the Pathogenesis to Clinical Management. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25158427"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1124\/pr.114.010090","article-title":"Toll-like Receptors in the Vascular System: Sensing the Dangers Within","volume":"68","author":"Goulopoulou","year":"2016","journal-title":"Pharmacol. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/s41392-021-00687-0","article-title":"Pattern Recognition Receptors in Health and Diseases","volume":"6","author":"Li","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e714","DOI":"10.1002\/mco2.714","article-title":"The Interaction of Innate Immune and Adaptive Immune System","volume":"5","author":"Wang","year":"2024","journal-title":"MedComm"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Chen, Y.-H., Wu, K.-H., and Wu, H.-P. (2024). Unraveling the Complexities of Toll-like Receptors: From Molecular Mechanisms to Clinical Applications. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25095037"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/s41392-025-02264-1","article-title":"Pattern Recognition Receptors: Function, Regulation and Therapeutic Potential","volume":"10","author":"Chen","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1111\/are.12607","article-title":"The Role of Toll-like Receptors in Innate Immunity and Infectious Diseases of Teleost","volume":"47","author":"Tanekhy","year":"2016","journal-title":"Aquac. Res."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Bhagwani, A., Thompson, A.A.R., and Farkas, L. (2020). When Innate Immunity Meets Angiogenesis\u2014The Role of Toll-Like Receptors in Endothelial Cells and Pulmonary Hypertension. Front. Med., 7.","DOI":"10.3389\/fmed.2020.00352"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"116671","DOI":"10.1016\/j.lfs.2019.116671","article-title":"TLRs in Pulmonary Diseases","volume":"233","author":"Arora","year":"2019","journal-title":"Life Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.bbrc.2012.08.106","article-title":"Viral Toll Like Receptor Activation of Pulmonary Vascular Smooth Muscle Cells Results in Endothelin-1 Generation; Relevance to Pathogenesis of Pulmonary Arterial Hypertension","volume":"426","author":"George","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/1476-9255-7-57","article-title":"The Role of Toll-like Receptors in Acute and Chronic Lung Inflammation","volume":"7","author":"Lafferty","year":"2010","journal-title":"J. Inflamm."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"397","DOI":"10.2741\/4396","article-title":"TLR4 Regulates Pulmonary Vascular Homeostasis and Remodeling via Redox Signaling","volume":"21","author":"Ma","year":"2016","journal-title":"Front. Biosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1164\/rccm.201606-1226PP","article-title":"Translational Advances in the Field of Pulmonary Hypertension.From Cancer Biology to New Pulmonary Arterial Hypertension Therapeutics. Targeting Cell Growth and Proliferation Signaling Hubs","volume":"195","author":"Pullamsetti","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1164\/rccm.201707-1370OC","article-title":"Toll-like Receptor 3 is a Therapeutic Target for Pulmonary Hypertension","volume":"199","author":"Farkas","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"105935","DOI":"10.1016\/j.isci.2023.105935","article-title":"A P53-TLR3 Axis Ameliorates Pulmonary Hypertension by Inducing BMPR2 via IRF3","volume":"26","author":"Bhagwani","year":"2023","journal-title":"iScience"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1189\/jlb.0812390","article-title":"Species-Specific PAMP Recognition by TLR2 and Evidence for Species-Restricted Interaction with Dectin-1","volume":"94","author":"Willcocks","year":"2013","journal-title":"J. Leukoc. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"672395","DOI":"10.1155\/2010\/672395","article-title":"DAMPening Inflammation by Modulating TLR Signalling","volume":"2010","author":"Piccinini","year":"2010","journal-title":"Mediat. Inflamm."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1016\/j.immuni.2024.03.002","article-title":"DAMPs and DAMP-Sensing Receptors in Inflammation and Diseases","volume":"57","author":"Ma","year":"2024","journal-title":"Immunity"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.immuni.2024.03.004","article-title":"Decoding Toll-like Receptors: Recent Insights and Perspectives in Innate Immunity","volume":"57","author":"Kawai","year":"2024","journal-title":"Immunity"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Curtin, J.F., Liu, N., Candolfi, M., Xiong, W., Assi, H., Yagiz, K., Edwards, M.R., Michelsen, K.S., Kroeger, K.M., and Liu, C. (2009). HMGB1 Mediates Endogenous TLR2 Activation and Brain Tumor Regression. PLoS Med., 6.","DOI":"10.1371\/journal.pmed.1000010"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Hsieh, M.L., Nishizaki, D., Adashek, J.J., Kato, S., and Kurzrock, R. (2025). Toll-like Receptor 3: A Double-Edged Sword. Biomark. Res., 13.","DOI":"10.1186\/s40364-025-00739-5"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"953","DOI":"10.2174\/0113894501316051240821060249","article-title":"Endogenous Ligands of TLR4 in Microglia: Potential Targets for Related Neurological Diseases","volume":"25","author":"Chen","year":"2024","journal-title":"Curr. Drug Targets"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1186\/s12964-023-01234-w","article-title":"TLR7 Activation by miR-21 Promotes Renal Fibrosis by Activating the pro-Inflammatory Signaling Pathway in Tubule Epithelial Cells","volume":"21","author":"Kim","year":"2023","journal-title":"Cell Commun. Signal."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"E2110","DOI":"10.1073\/pnas.1209414109","article-title":"MicroRNAs Bind to Toll-like Receptors to Induce Prometastatic Inflammatory Response","volume":"109","author":"Fabbri","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2479","DOI":"10.1182\/blood.2025028794","article-title":"Mitochondrial DNA via Recipient TLR9 Acts as a Potent First-Hit in Murine Transfusion-Related Acute Lung Injury (TRALI)","volume":"146","author":"Rebetz","year":"2025","journal-title":"Blood"},{"key":"ref_33","first-page":"96","article-title":"TLR10: An Intriguing Toll-Like Receptor with Many Unanswered Questions","volume":"16","author":"Rodrigues","year":"2024","journal-title":"J. Innate Immun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1513\/pats.201006-046WR","article-title":"Pathogenesis of HIV-Associated Pulmonary Hypertension","volume":"8","author":"Almodovar","year":"2011","journal-title":"Proc. Am. Thorac. Soc."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Butrous, G. (2025). Global Landscape of Infection-Induced Pulmonary Hypertension. Infect. Dis. Rep., 17.","DOI":"10.3390\/idr17020035"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1586\/ers.11.17","article-title":"Viral Infection and Pulmonary Hypertension: Is There an Association?","volume":"5","author":"Cool","year":"2011","journal-title":"Expert Rev. Respir. Med."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Castillo-Gal\u00e1n, S., Parra, V., and Cuenca, J. (2025). Unraveling the Pathogenesis of Viral-Induced Pulmonary Arterial Hypertension: Possible New Therapeutic Avenues with Mesenchymal Stromal Cells and Their Derivatives. Biochim. Biophys. Acta (BBA)-Mol. Basis Dis., 1871.","DOI":"10.1016\/j.bbadis.2024.167519"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Wang, D., Gomes, M.T., Mo, Y., Prohaska, C.C., Zhang, L., Chelvanambi, S., Clauss, M.A., Zhang, D., Machado, R.F., and Gao, M. (2023). Human Endogenous Retrovirus, SARS-CoV-2, and HIV Promote PAH via Inflammation and Growth Stimulation. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24087472"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Nie, L., Cai, S.-Y., Shao, J.-Z., and Chen, J. (2018). Toll-Like Receptors, Associated Biological Roles, and Signaling Networks in Non-Mammals. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01523"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Mertowski, S., Lipa, P., Morawska, I., Nied\u017awiedzka-Rystwej, P., B\u0119bnowska, D., Hrynkiewicz, R., Grywalska, E., Roli\u0144ski, J., and Za\u0142uska, W. (2020). Toll-Like Receptor as a Potential Biomarker in Renal Diseases. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186712"},{"key":"ref_41","unstructured":"(2025, September 11). UniProt. Available online: https:\/\/www.uniprot.org\/uniprotkb\/Q15399\/entry."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"11409","DOI":"10.1111\/jcmm.15745","article-title":"Transcriptomic Analysis Identifies Toll-like and Nod-like Pathways and Necroptosis in Pulmonary Arterial Hypertension","volume":"24","author":"Xiao","year":"2020","journal-title":"J. Cell Mol. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1002\/art.33325","article-title":"A Rare Polymorphism in the Gene for Toll-like Receptor 2 is Associated with Systemic Sclerosis Phenotype and Increases the Production of Inflammatory Mediators","volume":"64","author":"Broen","year":"2012","journal-title":"Arthritis Rheum."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"14.12.1","DOI":"10.1002\/0471142735.im1412s109","article-title":"Toll-like Receptors","volume":"109","author":"Takeda","year":"2015","journal-title":"Curr. Protoc. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"de Kivit, S., Tobin, M.C., Forsyth, C.B., Keshavarzian, A., and Landay, A.L. (2014). Regulation of Intestinal Immune Responses through TLR Activation: Implications for Pro- and Prebiotics. Front. Immunol., 5.","DOI":"10.3389\/fimmu.2014.00060"},{"key":"ref_46","unstructured":"(2025, September 11). UniProt. Available online: https:\/\/www.uniprot.org\/uniprotkb\/O60603\/entry."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1016\/j.cell.2007.09.008","article-title":"Crystal Structure of the TLR1-TLR2 Heterodimer Induced by Binding of a Tri-Acylated Lipopeptide","volume":"130","author":"Jin","year":"2007","journal-title":"Cell"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"S421","DOI":"10.1086\/431992","article-title":"The Role of Toll-like Receptors in the Regulation of Neutrophil Migration, Activation, and Apoptosis","volume":"41","author":"Sabroe","year":"2005","journal-title":"Clin. Infect. Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"S127","DOI":"10.1186\/ar567","article-title":"The Instructive Role of Dendritic Cells on T-Cell Responses","volume":"4","author":"Sallusto","year":"2002","journal-title":"Arthritis Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1567210","DOI":"10.1155\/2022\/1567210","article-title":"Macrophage Infiltration Initiates RIP3\/MLKL-Dependent Necroptosis in Paclitaxel-Induced Neuropathic Pain","volume":"2022","author":"Ma","year":"2022","journal-title":"Mediat. Inflamm."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Lian, G., You, J., Lin, W., Gao, G., Xu, C., Wang, H., and Luo, L. (2023). Bioinformatics Analysis of the Immune Cell Infiltration Characteristics and Correlation with Crucial Diagnostic Markers in Pulmonary Arterial Hypertension. BMC Pulm. Med., 23.","DOI":"10.1186\/s12890-023-02584-4"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/s41392-025-02287-8","article-title":"Signaling Pathways and Targeted Therapy for Pulmonary Hypertension","volume":"10","author":"Shi","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Wang, J., Uddin, M.N., Wang, R., Gong, Y., and Wu, Y. (2022). Comprehensive Analysis and Validation of Novel Immune and Vascular Remodeling Related Genes Signature Associated with Drug Interactions in Pulmonary Arterial Hypertension. Front. Genet., 13.","DOI":"10.3389\/fgene.2022.922213"},{"key":"ref_54","unstructured":"(2025, September 11). UniProt. Available online: https:\/\/www.uniprot.org\/uniprotkb\/O15455\/entry."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Kim, J.H., Song, D.H., Youn, S.-J., Kim, J.W., Cho, G., Kim, S.C., Lee, H., Jin, M.S., and Lee, J.-O. (2016). Crystal Structures of Mono- and Bi-Specific Diabodies and Reduction of Their Structural Flexibility by Introduction of Disulfide Bridges at the Fv Interface. Sci. Rep., 6.","DOI":"10.1038\/srep34515"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3533","DOI":"10.1073\/pnas.0308496101","article-title":"Toll-like Receptor 3-Mediated Activation of NF-kappaB and IRF3 Diverges at Toll-IL-1 Receptor Domain-Containing Adapter Inducing IFN-Beta","volume":"101","author":"Jiang","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1631\/jzus.B2000808","article-title":"Toll-like Receptor 3 (TLR3) Regulation Mechanisms and Roles in Antiviral Innate Immune Responses","volume":"22","author":"Chen","year":"2021","journal-title":"J. Zhejiang Univ. Sci. B"},{"key":"ref_58","first-page":"297","article-title":"The Functional Mechanisms of Toll-Like Receptor 3 and Its Implications in Digestive System Tumors","volume":"28","author":"Han","year":"2023","journal-title":"FBL"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1038\/sj.cdd.4401850","article-title":"TLR Signaling","volume":"13","author":"Kawai","year":"2006","journal-title":"Cell Death Differ."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2751","DOI":"10.1007\/s00018-020-03453-7","article-title":"Infection and Atherosclerosis: TLR-Dependent Pathways","volume":"77","author":"Li","year":"2020","journal-title":"Cell Mol. Life Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.atherosclerosis.2013.03.035","article-title":"TLR3 Deficiency Protects against Collagen Degradation and Medial Destruction in Murine Atherosclerotic Plaques","volume":"229","author":"Ishibashi","year":"2013","journal-title":"Atherosclerosis"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Pan, L., Zhu, W., Li, Y., Xu, X., Guo, L., Lu, Q., and Wang, J. (2014). Astrocytic Toll-Like Receptor 3 is Associated with Ischemic Preconditioning- Induced Protection against Brain Ischemia in Rodents. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0099526"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2372","DOI":"10.1073\/pnas.1018515108","article-title":"Unexpected Protective Role for Toll-like Receptor 3 in the Arterial Wall","volume":"108","author":"Cole","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1016\/j.tips.2022.05.004","article-title":"Toll-like Receptor-Mediated Neuroinflammation: Relevance for Cognitive Dysfunctions","volume":"43","author":"Squillace","year":"2022","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"20446","DOI":"10.1073\/pnas.0810372105","article-title":"A Critical Link between Toll-like Receptor 3 and Type II Interferon Signaling Pathways in Antiviral Innate Immunity","volume":"105","author":"Negishi","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s00018-022-04219-z","article-title":"Type I Interferon-Mediated Tumor Immunity and Its Role in Immunotherapy","volume":"79","author":"Yu","year":"2022","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"18","DOI":"10.33963\/v.phj.104053","article-title":"Emerging Therapies and New Directions in the Treatment of Pulmonary Arterial Hypertension","volume":"83","author":"Skride","year":"2025","journal-title":"Pol. Heart J."},{"key":"ref_68","unstructured":"(2025, September 12). UniProt. Available online: https:\/\/www.uniprot.org\/uniprotkb\/O00206\/entry."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s12979-023-00383-3","article-title":"Toll-like Receptor 4 (TLR4): New Insight Immune and Aging","volume":"20","author":"Kim","year":"2023","journal-title":"Immun. Ageing"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Duan, T., Du, Y., Xing, C., Wang, H.Y., and Wang, R.-F. (2022). Toll-Like Receptor Signaling and Its Role in Cell-Mediated Immunity. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.812774"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"66656","DOI":"10.18632\/oncotarget.19105","article-title":"The Role of Toll-like Receptor 4 in Tumor Microenvironment","volume":"8","author":"Li","year":"2017","journal-title":"Oncotarget"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Oda, M., Yamamoto, H., and Kawakami, T. (2024). Maintenance of Homeostasis by TLR4 Ligands. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1286270"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Wei, J., Zhang, Y., Li, H., Wang, F., and Yao, S. (2023). Toll-like Receptor 4: A Potential Therapeutic Target for Multiple Human Diseases. Biomed. Pharmacother., 166.","DOI":"10.1016\/j.biopha.2023.115338"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Mansouri, A., Akthar, I., and Miyamoto, A. (2025). TLR2 and TLR4 Bridge Physiological and Pathological Inflammation in the Reproductive System. Commun. Biol., 8.","DOI":"10.1038\/s42003-025-08424-x"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"611","DOI":"10.3892\/etm.2016.3425","article-title":"MyD88-Dependent Toll-like Receptor 4 Signal Pathway in Intervertebral Disc Degeneration","volume":"12","author":"Qin","year":"2016","journal-title":"Exp. Ther. Med."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Chettab, K., Fitzsimmons, C., Novikov, A., Denis, M., Phelip, C., Math\u00e9, D., Choffour, P.A., Beaumel, S., Fourmaux, E., and Norca, P. (2023). A Systemically Administered Detoxified TLR4 Agonist Displays Potent Antitumor Activity and an Acceptable Tolerance Profile in Preclinical Models. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1066402"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Richert, I., Berchard, P., Abbes, L., Novikov, A., Chettab, K., Vandermoeten, A., Dumontet, C., Karanian, M., Kerzerho, J., and Caroff, M. (2023). A TLR4 Agonist Induces Osteosarcoma Regression by Inducing an Antitumor Immune Response and Reprogramming M2 Macrophages to M1 Macrophages. Cancers, 15.","DOI":"10.3390\/cancers15184635"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Gabr, M.M., Saeed, I., Miles, J.A., Ross, B.P., Shaw, P.N., Hollmann, M.W., and Parat, M.-O. (2021). Interaction of Opioids with TLR4\u2014Mechanisms and Ramifications. Cancers, 13.","DOI":"10.3390\/cancers13215274"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Li, Y., Sun, L., Zhou, Q., Lee, A.J., Wang, L., Zhang, R., and Wang, S. (2024). Effects of Opioid Drugs on Immune Function in Cancer Patients. Biomed. Pharmacother., 175.","DOI":"10.1016\/j.biopha.2024.116665"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e839","DOI":"10.1002\/iid3.839","article-title":"Toll-like Receptors in Pathogenesis of Neurodegenerative Diseases and Their Therapeutic Potential","volume":"11","author":"Dabi","year":"2023","journal-title":"Immun. Inflamm. Dis."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/s41392-023-01486-5","article-title":"Role of Neuroinflammation in Neurodegeneration Development","volume":"8","author":"Zhang","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.bbi.2020.10.007","article-title":"Role of Astroglial Toll-like Receptors (TLRs) in Central Nervous System Infections, Injury and Neurodegenerative Diseases","volume":"91","author":"Li","year":"2021","journal-title":"Brain Behav. Immun."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Fu, Y., Gong, T., Loughran, P.A., Li, Y., Billiar, T.R., Liu, Y., Wen, Z., and Fan, J. (2025). Roles of TLR4 in Macrophage Immunity and Macrophage-Pulmonary Vascular\/Lymphatic Endothelial Cell Interactions in Sepsis. Commun. Biol., 8.","DOI":"10.1038\/s42003-025-07921-3"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Stierschneider, A., and Wiesner, C. (2023). Shedding Light on the Molecular and Regulatory Mechanisms of TLR4 Signaling in Endothelial Cells under Physiological and Inflamed Conditions. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1264889"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1161\/CIRCRESAHA.114.303945","article-title":"Platelet TLR4, a Critical Link in Pulmonary Arterial Hypertension","volume":"114","author":"Sun","year":"2014","journal-title":"Circ. Res."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Dai, J., Chen, H., Fang, J., Wu, S., and Jia, Z. (2025). Vascular Remodeling: The Multicellular Mechanisms of Pulmonary Hypertension. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26094265"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Ye, Y., Xu, Q., and Wuren, T. (2023). Inflammation and Immunity in the Pathogenesis of Hypoxic Pulmonary Hypertension. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1162556"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"3612","DOI":"10.1021\/jm401006s","article-title":"Toll-like Receptor 4 (TLR4) Modulation by Synthetic and Natural Compounds: An Update","volume":"57","author":"Peri","year":"2014","journal-title":"J. Med. Chem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2486829","DOI":"10.1080\/10641963.2025.2486829","article-title":"Cinnamaldehyde Alleviates Pulmonary Hypertension by Affecting Vascular Remodeling through the TLR4\/NF-kB\/HIF-1a Pathway","volume":"47","author":"Zhang","year":"2025","journal-title":"Clin. Exp. Hypertens."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"9605894","DOI":"10.1155\/2017\/9605894","article-title":"Toll-Like Receptor 4 Signalling and Its Impact on Platelet Function, Thrombosis, and Haemostasis","volume":"2017","author":"Vallance","year":"2017","journal-title":"Mediat. Inflamm."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1161\/CIRCRESAHA.114.303662","article-title":"Genetic Deletion of Toll-like Receptor 4 on Platelets Attenuates Experimental Pulmonary Hypertension","volume":"114","author":"Bauer","year":"2014","journal-title":"Circ. Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.vph.2018.12.006","article-title":"HMGB1\/TLR4 Promotes Hypoxic Pulmonary Hypertension via Suppressing BMPR2 Signaling","volume":"117","author":"Wang","year":"2019","journal-title":"Vasc. Pharmacol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1164\/rccm.201902-0388ED","article-title":"A Novel Peptide for Immunomodulation in Pulmonary Arterial Hypertension","volume":"199","author":"Grinnan","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Huang, L., Zhang, H., Liu, Y., and Long, Y. (2022). The Role of Gut and Airway Microbiota in Pulmonary Arterial Hypertension. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.929752"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Wedgwood, S., Gerard, K., Halloran, K., Hanhauser, A., Monacelli, S., Warford, C., Thai, P.N., Chiamvimonvat, N., Lakshminrusimha, S., and Steinhorn, R.H. (2020). Intestinal Dysbiosis and the Developing Lung: The Role of Toll-Like Receptor 4 in the Gut-Lung Axis. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.00357"},{"key":"ref_96","unstructured":"(2025, September 12). UniProt. Available online: https:\/\/www.uniprot.org\/uniprotkb\/O60602\/entry."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"12487","DOI":"10.1073\/pnas.0605200103","article-title":"Involvement of Toll-like Receptor 5 in the Recognition of Flagellated Bacteria","volume":"103","author":"Feuillet","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"23624","DOI":"10.1074\/jbc.M303481200","article-title":"Identification of a Sequence in Human Toll-like Receptor 5 Required for the Binding of Gram-Negative Flagellin","volume":"278","author":"Mizel","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Amemiya, K., Dankmeyer, J.L., Bernhards, R.C., Fetterer, D.P., Waag, D.M., Worsham, P.L., and DeShazer, D. (2021). Activation of Toll-Like Receptors by Live Gram-Negative Bacterial Pathogens Reveals Mitigation of TLR4 Responses and Activation of TLR5 by Flagella. Front. Cell. Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.745325"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Tallant, T., Deb, A., Kar, N., Lupica, J., de Veer, M.J., and DiDonato, J.A. (2004). Flagellin Acting via TLR5 is the Major Activator of Key Signaling Pathways Leading to NF-\u03baB and Proinflammatory Gene Program Activation in Intestinal Epithelial Cells. BMC Microbiol., 4.","DOI":"10.1186\/1471-2180-4-33"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"e005111","DOI":"10.1136\/bmjdrc-2025-005111","article-title":"TLR5 Influences the Development of Type 1 Diabetes","volume":"13","author":"Buschard","year":"2025","journal-title":"BMJ Open Diabetes Res. Care"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2491","DOI":"10.2147\/JIR.S407521","article-title":"TLR5 Signaling in the Regulation of Intestinal Mucosal Immunity","volume":"16","author":"Feng","year":"2023","journal-title":"J. Inflamm. Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"475","DOI":"10.4049\/jimmunol.1102977","article-title":"TLR5; a Novel and Unidentified Inflammatory Mediator in Rheumatoid Arthritis That Correlates with Disease Activity Score and Joint TNF-\u03b1 Levels","volume":"189","author":"Chamberlain","year":"2012","journal-title":"J. Immunol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.intimp.2018.03.002","article-title":"Toll-like Receptors in Immunity and Inflammatory Diseases: Past, Present, and Future","volume":"59","author":"Vijay","year":"2018","journal-title":"Int. Immunopharmacol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"e549","DOI":"10.1002\/mco2.549","article-title":"Toll-like Receptors in Health and Disease","volume":"5","author":"Wang","year":"2024","journal-title":"MedComm"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2466","DOI":"10.1158\/0008-5472.CAN-10-1993","article-title":"Activation of Toll-Like Receptor 5 on Breast Cancer Cells by Flagellin Suppresses Cell Proliferation and Tumor Growth","volume":"71","author":"Cai","year":"2011","journal-title":"Cancer Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1158\/2326-6066.CIR-24-0513","article-title":"TLR5 Signaling Causes Dendritic Cell Dysfunction and Orchestrates Failure of Immune Checkpoint Therapy against Ovarian Cancer","volume":"13","author":"McGinty","year":"2025","journal-title":"Cancer Immunol. Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/s12276-019-0275-6","article-title":"The Flagellin-TLR5-Nox4 Axis Promotes the Migration of Smooth Muscle Cells in Atherosclerosis","volume":"51","author":"Kim","year":"2019","journal-title":"Exp. Mol. Med."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Kim, J., Seo, M., Kim, S.K., and Bae, Y.S. (2016). Flagellin-Induced NADPH Oxidase 4 Activation is Involved in Atherosclerosis. Sci. Rep., 6.","DOI":"10.1038\/srep25437"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Ellenbroek, G.H.J.M., van Puijvelde, G.H.M., Anas, A.A., Bot, M., Asbach, M., Schoneveld, A., van Santbrink, P.J., Foks, A.C., Timmers, L., and Doevendans, P.A. (2017). Leukocyte TLR5 Deficiency Inhibits Atherosclerosis by Reduced Macrophage Recruitment and Defective T-Cell Responsiveness. Sci. Rep., 7.","DOI":"10.1038\/srep42688"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1038\/s41419-019-2187-8","article-title":"TLR5: A Prognostic and Monitoring Indicator for Triple-Negative Breast Cancer","volume":"10","author":"Shi","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ccell.2014.12.008","article-title":"Common TLR5 Mutations Control Cancer Progression","volume":"27","author":"Pfirschke","year":"2015","journal-title":"Cancer Cell"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"497","DOI":"10.3233\/CH-180529","article-title":"Cellular Inflammation in Pulmonary Hypertension: Detailed Analysis of Lung and Right Ventricular Tissue, Circulating Immune Cells and Effects of a Dual Endothelin Receptor Antagonist","volume":"73","author":"Rohm","year":"2019","journal-title":"Clin. Hemorheol. Microcirc."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Sakamachi, Y., Wiley, E., Solis, A., Johnson, C.G., Meng, X., Hussain, S., Lipinski, J.H., O\u2019Dwyer, D.N., Randall, T., and Malphurs, J. (2024). Toll-Like-Receptor 5 Protects against Pulmonary Fibrosis by Reducing Lung Dysbiosis. bioRxiv, bioRxiv:2024.04.30.591719.","DOI":"10.1101\/2024.04.30.591719"},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Oh, S., Jang, A.Y., Chae, S., Choi, S., Moon, J., Kim, M., Spiekerkoetter, E., Zamanian, R.T., Yang, P.C., and Hwang, D. (2021). Comparative Analysis on the Anti-Inflammatory\/Immune Effect of Mesenchymal Stem Cell Therapy for the Treatment of Pulmonary Arterial Hypertension. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-81244-1"},{"key":"ref_116","unstructured":"(2025, September 12). UniProt. Available online: https:\/\/www.uniprot.org\/uniprotkb\/Q9Y2C9\/entry."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"3305","DOI":"10.1016\/j.jmb.2014.07.024","article-title":"Crystal Structure of TIR Domain of TLR6 Reveals Novel Dimeric Interface of TIR-TIR Interaction for Toll-like Receptor Signaling Pathway","volume":"426","author":"Jang","year":"2014","journal-title":"J. Mol. Biol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1038\/gene.2013.34","article-title":"A TLR6 Polymorphism is Associated with Increased Risk of Legionnaires\u2019 Disease","volume":"14","author":"Misch","year":"2013","journal-title":"Genes Immun."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Hoffjan, S., Stemmler, S., Parwez, Q., Petrasch-Parwez, E., Arinir, U., Rohde, G., Reinitz-Rademacher, K., Schultze-Werninghaus, G., Bufe, A., and Epplen, J.T. (2005). Evaluation of the Toll-like Receptor 6 Ser249Pro Polymorphism in Patients with Asthma, Atopic Dermatitis and Chronic Obstructive Pulmonary Disease. BMC Med. Genet., 6.","DOI":"10.1186\/1471-2350-6-34"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"66","DOI":"10.22203\/eCM.v026a05","article-title":"Toll-like Receptor 2\/6-Dependent Stimulation of Mesenchymal Stem Cells Promotes Angiogenesis by Paracrine Factors","volume":"26","author":"Grote","year":"2013","journal-title":"Eur. Cell Mater."},{"key":"ref_121","unstructured":"(2025, September 12). UniProt. Available online: https:\/\/www.uniprot.org\/uniprotkb\/Q9NYK1\/entry."},{"key":"ref_122","unstructured":"(2025, September 12). UniProt. Available online: https:\/\/www.uniprot.org\/uniprotkb\/Q9NR97\/entry."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.virol.2011.02.003","article-title":"Innate Immune Sensing of DNA Viruses","volume":"411","author":"Rathinam","year":"2011","journal-title":"Virology"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"100406","DOI":"10.1016\/j.microb.2025.100406","article-title":"Identification of Single Stranded RNA Fragments Recognised by TLR7\/8 in Dengue and Other Mosquito-Borne Flaviviral Genomes: A Bioinformatics Approach","volume":"7","author":"Bello","year":"2025","journal-title":"Microbe"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Soleiman-Meigooni, S., Yarahmadi, A., Kheirkhah, A.-H., and Afkhami, H. (2024). Recent Advances in Different Interactions between Toll-like Receptors and Hepatitis B Infection: A Review. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1363996"},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Wen, L., Zhang, B., Wu, X., Liu, R., Fan, H., Han, L., Zhang, Z., Ma, X., Chu, C.-Q., and Shi, X. (2023). Toll-like Receptors 7 and 9 Regulate the Proliferation and Differentiation of B Cells in Systemic Lupus Erythematosus. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1093208"},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Sakata, K., Nakayamada, S., Miyazaki, Y., Kubo, S., Ishii, A., Nakano, K., and Tanaka, Y. (2018). Up-Regulation of TLR7-Mediated IFN-\u03b1 Production by Plasmacytoid Dendritic Cells in Patients With Systemic Lupus Erythematosus. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01957"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"3045","DOI":"10.1038\/s41467-025-58220-8","article-title":"Type III Interferon Primes pDCs for TLR7 Activation and Antagonizes Immune Suppression Mediated by TGF-\u03b2 and PGE2","volume":"16","author":"Sakref","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1042\/BJ20090013","article-title":"NF-\u03baB Activation Primes Cells to a pro-Inflammatory Polarized Response to a TLR7 Agonist","volume":"421","author":"Lee","year":"2009","journal-title":"Biochem. J."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1111\/imr.12381","article-title":"Negative Regulation of TLR Signaling in Myeloid Cells\u2014Implications for Autoimmune Diseases","volume":"269","author":"Hamerman","year":"2016","journal-title":"Immunol. Rev."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/cmi.2012.38","article-title":"TLR8: The Forgotten Relative Revindicated","volume":"9","author":"Cervantes","year":"2012","journal-title":"Cell Mol. Immunol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/nri3665","article-title":"Innate Immunity to Influenza Virus Infection","volume":"14","author":"Iwasaki","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/ni0602-499","article-title":"Human TLR7 or TLR8 Independently Confer Responsiveness to the Antiviral Compound R-848","volume":"3","author":"Jurk","year":"2002","journal-title":"Nat. Immunol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s00251-020-01165-7","article-title":"COVID-19 Pandemic: Is a Gender-Defined Dosage Effect Responsible for the High Mortality Rate among Males?","volume":"72","author":"Bontrop","year":"2020","journal-title":"Immunogenetics"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1002\/art.38298","article-title":"Epicutaneous Application of Toll-like Receptor 7 Agonists Leads to Systemic Autoimmunity in Wild-Type Mice: A New Model of Systemic Lupus Erythematosus","volume":"66","author":"Yokogawa","year":"2014","journal-title":"Arthritis Rheumatol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"2300204","DOI":"10.1183\/13993003.00204-2023","article-title":"TLR7\/8 Activation Induces Autoimmune Vasculopathy and Causes Severe Pulmonary Arterial Hypertension","volume":"62","author":"Yeh","year":"2023","journal-title":"Eur. Respir. J."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"7485","DOI":"10.4049\/jimmunol.172.12.7485","article-title":"Rat Plasmacytoid Dendritic Cells Are an Abundant Subset of MHC Class II+ CD4+CD11b-OX62- and Type I IFN-Producing Cells That Exhibit Selective Expression of Toll-like Receptors 7 and 9 and Strong Responsiveness to CpG","volume":"172","author":"Hubert","year":"2004","journal-title":"J. Immunol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.1378\/chest.14-1678","article-title":"T-Helper 17 Cell Polarization in Pulmonary Arterial Hypertension","volume":"147","author":"Hautefort","year":"2015","journal-title":"Chest"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"156534","DOI":"10.1016\/j.cyto.2024.156534","article-title":"Th17\/IL-17A Axis is Critical for Pulmonary Arterial Hypertension (PAH) in Systemic Sclerosis (SSc): SSc Patients with High Levels of Serum IL-17A Exhibit Reduced Lung Functions and Increased Prevalence of PAH","volume":"176","author":"Seki","year":"2024","journal-title":"Cytokine"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1016\/j.chest.2016.01.004","article-title":"Regulatory T Cell Dysfunction in Idiopathic, Heritable and Connective Tissue-Associated Pulmonary Arterial Hypertension","volume":"149","author":"Huertas","year":"2016","journal-title":"Chest"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1097\/HJH.0000000000002368","article-title":"Toll-like Receptor 7-Driven Lupus Autoimmunity Induces Hypertension and Vascular Alterations in Mice","volume":"38","author":"Toral","year":"2020","journal-title":"J. Hypertens."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.autrev.2017.01.007","article-title":"Gender Balance in Patients with Systemic Lupus Erythematosus","volume":"16","author":"Bundell","year":"2017","journal-title":"Autoimmun. Rev."},{"key":"ref_143","unstructured":"(2025, September 12). UniProt. Available online: https:\/\/www.uniprot.org\/uniprotkb\/Q9NR96\/entry."},{"key":"ref_144","first-page":"145","article-title":"Bacterial CpG-DNA Licenses TLR9","volume":"270","author":"Bauer","year":"2002","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1038\/nature14138","article-title":"Structural Basis of CpG and Inhibitory DNA Recognition by Toll-like Receptor 9","volume":"520","author":"Ohto","year":"2015","journal-title":"Nature"},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Ding, Z., Liu, S., Wang, X., Khaidakov, M., Dai, Y., and Mehta, J.L. (2013). Oxidant Stress in Mitochondrial DNA Damage, Autophagy and Inflammation in Atherosclerosis. Sci. Rep., 3.","DOI":"10.1038\/srep01077"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1097\/SHK.0000000000000601","article-title":"Toll-Like Receptor-9 (TLR9) Is Requisite for Acute Inflammatory Response and Injury Following Lung Contusion","volume":"46","author":"Suresh","year":"2016","journal-title":"Shock"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.1681\/ASN.2015040376","article-title":"Role of Mitochondrial DNA in Septic AKI via Toll-Like Receptor 9","volume":"27","author":"Tsuji","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"L962","DOI":"10.1152\/ajplung.00073.2014","article-title":"Mitochondria in Lung Biology and Pathology: More than Just a Powerhouse","volume":"306","author":"Schumacker","year":"2014","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1172\/JCI83885","article-title":"Hepatocyte Mitochondrial DNA Drives Nonalcoholic Steatohepatitis by Activation of TLR9","volume":"126","author":"Santoro","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.4049\/jimmunol.1800211","article-title":"Kidney Proximal Tubular TLR9 Exacerbates Ischemic Acute Kidney Injury","volume":"201","author":"Han","year":"2018","journal-title":"J. Immunol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1093\/cvr\/cvv137","article-title":"Circulating Mitochondrial DNA and Toll-like Receptor 9 Are Associated with Vascular Dysfunction in Spontaneously Hypertensive Rats","volume":"107","author":"McCarthy","year":"2015","journal-title":"Cardiovasc. Res."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/nature10992","article-title":"Mitochondrial DNA That Escapes from Autophagy Causes Inflammation and Heart Failure","volume":"485","author":"Oka","year":"2012","journal-title":"Nature"},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Loomis, Z., Eigenberger, P., Redinius, K., Lisk, C., Karoor, V., Nozik-Grayck, E., Ferguson, S.K., Hassell, K., Nuss, R., and Stenmark, K. (2017). Hemoglobin Induced Cell Trauma Indirectly Influences Endothelial TLR9 Activity Resulting in Pulmonary Vascular Smooth Muscle Cell Activation. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0173652"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"e019247","DOI":"10.1161\/JAHA.120.019247","article-title":"Chronic Inhibition of Toll-Like Receptor 9 Ameliorates Pulmonary Hypertension in Rats","volume":"10","author":"Ishikawa","year":"2021","journal-title":"J. Am. Heart Assoc."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1093\/cvr\/cvw070","article-title":"Haemodynamic Unloading Reverses Occlusive Vascular Lesions in Severe Pulmonary Hypertension","volume":"111","author":"Abe","year":"2016","journal-title":"Cardiovasc. Res."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1182\/blood-2015-06-649491","article-title":"Revisiting the Hyperhemolysis Paradigm","volume":"126","author":"Gladwin","year":"2015","journal-title":"Blood"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"2254","DOI":"10.1056\/NEJMra0804411","article-title":"Pulmonary Complications of Sickle Cell Disease","volume":"359","author":"Gladwin","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1111\/j.1365-2141.2009.08004.x","article-title":"Pleiotropic Effects of Intravascular Hemolysis on Vascular Homeostasis","volume":"148","author":"Kato","year":"2010","journal-title":"Br. J. Haematol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1182\/asheducation-2008.1.186","article-title":"Novel Small Molecule Therapeutics for Sickle Cell Disease: Nitric Oxide, Carbon Monoxide, Nitrite, and Apolipoprotein A-I","volume":"2008","author":"Kato","year":"2008","journal-title":"Hematol. Am. Soc. Hematol. Educ. Program"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"2024","DOI":"10.1016\/j.jacc.2009.12.046","article-title":"Novel Biomarkers, Oxidative Stress, and the Role of Labile Iron Toxicity in Cardiopulmonary Bypass-Associated Acute Kidney Injury","volume":"55","author":"Haase","year":"2010","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1165\/rcmb.2012-0440OC","article-title":"Hemoglobin-Induced Endothelial Cell Permeability is Controlled, in Part, via a Myeloid Differentiation Primary Response Gene-88-Dependent Signaling Mechanism","volume":"49","author":"Lisk","year":"2013","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"29582","DOI":"10.1074\/jbc.M109.045344","article-title":"Oxidized Hemoglobin is an Endogenous Proinflammatory Agonist That Targets Vascular Endothelial Cells","volume":"284","author":"Silva","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"L532","DOI":"10.1152\/ajplung.00155.2015","article-title":"Cell-Free Hemoglobin: A Novel Mediator of Acute Lung Injury","volume":"310","author":"Shaver","year":"2016","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"Schaer, D.J., Vinchi, F., Ingoglia, G., Tolosano, E., and Buehler, P.W. (2014). Haptoglobin, Hemopexin, and Related Defense Pathways-Basic Science, Clinical Perspectives, and Drug Development. Front. Physiol., 5.","DOI":"10.3389\/fphys.2014.00415"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"a013433","DOI":"10.1101\/cshperspect.a013433","article-title":"Cell-Free Hemoglobin and Its Scavenger Proteins: New Disease Models Leading the Way to Targeted Therapies","volume":"3","author":"Schaer","year":"2013","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Smith, A., and McCulloh, R.J. (2015). Hemopexin and Haptoglobin: Allies against Heme Toxicity from Hemoglobin Not Contenders. Front. Physiol., 6.","DOI":"10.3389\/fphys.2015.00187"},{"key":"ref_168","unstructured":"(2025, September 12). UniProt. Available online: https:\/\/www.uniprot.org\/uniprotkb\/Q9BXR5\/entry."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"E4478","DOI":"10.1073\/pnas.1410293111","article-title":"Human TLR10 is an Anti-Inflammatory Pattern-Recognition Receptor","volume":"111","author":"Oosting","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"e12988","DOI":"10.1111\/sji.12988","article-title":"TLR10: Insights, Controversies and Potential Utility as a Therapeutic Target","volume":"93","author":"Su","year":"2021","journal-title":"Scand. J. Immunol."},{"key":"ref_171","doi-asserted-by":"crossref","unstructured":"Henrick, B.M., Yao, X.-D., Zahoor, M.A., Abimiku, A., Osawe, S., and Rosenthal, K.L. (2019). TLR10 Senses HIV-1 Proteins and Significantly Enhances HIV-1 Infection. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00482"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"11861","DOI":"10.1074\/jbc.C800001200","article-title":"The Crystal Structure of the Human Toll-like Receptor 10 Cytoplasmic Domain Reveals a Putative Signaling Dimer","volume":"283","author":"Nyman","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"5094","DOI":"10.4049\/jimmunol.0901888","article-title":"Human TLRs 10 and 1 Share Common Mechanisms of Innate Immune Sensing but Not Signaling","volume":"184","author":"Guan","year":"2010","journal-title":"J. Immunol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S0167-4781(00)00289-X","article-title":"Identification of hTLR10: A Novel Human Toll-like Receptor Preferentially Expressed in Immune Cells","volume":"1518","author":"Chuang","year":"2001","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"4531","DOI":"10.4049\/jimmunol.168.9.4531","article-title":"Quantitative Expression of Toll-like Receptor 1-10 mRNA in Cellular Subsets of Human Peripheral Blood Mononuclear Cells and Sensitivity to CpG Oligodeoxynucleotides","volume":"168","author":"Hornung","year":"2002","journal-title":"J. Immunol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"6084","DOI":"10.4049\/jimmunol.1203245","article-title":"Identification of TLR10 as a Key Mediator of the Inflammatory Response to Listeria Monocytogenes in Intestinal Epithelial Cells and Macrophages","volume":"191","author":"Regan","year":"2013","journal-title":"J. Immunol."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1093\/infdis\/jiv270","article-title":"Toll-like Receptor 10 in Helicobacter Pylori Infection","volume":"212","author":"Nagashima","year":"2015","journal-title":"J. Infect. Dis."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"5341","DOI":"10.1007\/s00253-021-11406-8","article-title":"Research Progress on Toll-like Receptor Signal Transduction and Its Roles in Antimicrobial Immune Responses","volume":"105","author":"Xia","year":"2021","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_179","doi-asserted-by":"crossref","unstructured":"Neuper, T., Frauenlob, T., Sarajlic, M., Posselt, G., Wessler, S., and Horejs-Hoeck, J. (2020). TLR2, TLR4 and TLR10 Shape the Cytokine and Chemokine Release of H. Pylori-Infected Human DCs. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21113897"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/j.1469-0691.2010.03285.x","article-title":"Inflammation, Immunological Reaction and Role of Infection in Pulmonary Hypertension","volume":"17","author":"Pullamsetti","year":"2011","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_181","doi-asserted-by":"crossref","unstructured":"Tomaszewski, M., B\u0119bnowska, D., Hrynkiewicz, R., Dworzy\u0144ski, J., Nied\u017awiedzka-Rystwej, P., Kope\u0107, G., and Grywalska, E. (2021). Role of the Immune System Elements in Pulmonary Arterial Hypertension. J. Clin. Med., 10.","DOI":"10.3390\/jcm10163757"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/s41392-020-00376-4","article-title":"Targeting the Signaling in Epstein\u2013Barr Virus-Associated Diseases: Mechanism, Regulation, and Clinical Study","volume":"6","author":"Cao","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1186\/s12985-023-02187-9","article-title":"Epstein-Barr Virus Infection: The Micro and Macro Worlds","volume":"20","author":"Huang","year":"2023","journal-title":"Virol. J."},{"key":"ref_184","doi-asserted-by":"crossref","unstructured":"Silva, J.D.M., Alves, C.E.d.C., and Pontes, G.S. (2024). Epstein-Barr Virus: The Mastermind of Immune Chaos. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1297994"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"142","DOI":"10.26444\/jpccr\/81214","article-title":"Epstein-Barr Virus\u2014Pathogenesis, Latency and Cancers","volume":"11","author":"Kliszczewska","year":"2017","journal-title":"J. Pre-Clin. Clin. Res."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1186\/s12985-017-0891-5","article-title":"Interferon-\u03b3-Inducible Protein 16 (IFI16) is Required for the Maintenance of Epstein-Barr Virus Latency","volume":"14","author":"Pisano","year":"2017","journal-title":"Virol. J."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"8606","DOI":"10.1128\/JVI.00805-13","article-title":"Constitutive Interferon-Inducible Protein 16-Inflammasome Activation during Epstein-Barr Virus Latency I, II, and III in B and Epithelial Cells","volume":"87","author":"Ansari","year":"2013","journal-title":"J. Virol."},{"key":"ref_188","doi-asserted-by":"crossref","unstructured":"Kurakula, K., Smolders, V.F.E.D., Tura-Ceide, O., Jukema, J.W., Quax, P.H.A., and Goumans, M.-J. (2021). Endothelial Dysfunction in Pulmonary Hypertension: Cause or Consequence?. Biomedicines, 9.","DOI":"10.3390\/biomedicines9010057"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"119","DOI":"10.2169\/internalmedicine.50.4143","article-title":"Pulmonary Arterial Hypertension Associated with Chronic Active Epstein-Barr Virus Infection","volume":"50","author":"Hashimoto","year":"2011","journal-title":"Intern. Med."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.jiac.2022.10.013","article-title":"Chronic Active Epstein-Bar Virus Infection Complicated by Pulmonary Artery Hypertension","volume":"29","author":"Misaki","year":"2023","journal-title":"J. Infect. Chemother."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1111\/ped.12578","article-title":"Pulmonary Arterial Hypertension Associated with Chronic Active Epstein-Barr Virus Infection","volume":"57","author":"Fukuda","year":"2015","journal-title":"Pediatr. Int."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"240805","DOI":"10.1155\/2011\/240805","article-title":"Ganciclovir Antiviral Therapy in Advanced Idiopathic Pulmonary Fibrosis: An Open Pilot Study","volume":"2011","author":"Egan","year":"2011","journal-title":"Pulm. Med."},{"key":"ref_193","doi-asserted-by":"crossref","unstructured":"Calabrese, F., Kipar, A., Lunardi, F., Balestro, E., Perissinotto, E., Rossi, E., Nannini, N., Marulli, G., Stewart, J.P., and Rea, F. (2013). Herpes Virus Infection is Associated with Vascular Remodeling and Pulmonary Hypertension in Idiopathic Pulmonary Fibrosis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0055715"},{"key":"ref_194","doi-asserted-by":"crossref","unstructured":"Duckworth, A., Longhurst, H.J., Paxton, J.K., and Scotton, C.J. (2021). The Role of Herpes Viruses in Pulmonary Fibrosis. Front. Med., 8.","DOI":"10.3389\/fmed.2021.704222"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.rmr.2011.09.050","article-title":"HIV-related pulmonary arterial hypertension","volume":"29","author":"Savale","year":"2012","journal-title":"Rev. Mal. Respir."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"101479","DOI":"10.1016\/j.cegh.2023.101479","article-title":"To Estimate Prevalence of Pulmonary Arterial Hypertension in HIV Patients and Its Association with CD4 Cell Count","volume":"25","author":"Mahajan","year":"2024","journal-title":"Clin. Epidemiol. Glob. Health"},{"key":"ref_197","doi-asserted-by":"crossref","unstructured":"\u0218oldea, S., Iov\u0103nescu, M., Berceanu, M., Mirea, O., Raicea, V., Bezn\u0103, M.C., Roc\u0219oreanu, A., and Donoiu, I. (2025). Cardiovascular Disease in HIV Patients: A Comprehensive Review of Current Knowledge and Clinical Implications. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26051837"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1016\/S0046-8177(87)80417-3","article-title":"Membranoproliferative Glomerulonephritis and Plexogenic Pulmonary Arteriopathy in a Homosexual Man with Acquired Immunodeficiency Syndrome","volume":"18","author":"Kim","year":"1987","journal-title":"Hum. Pathol."},{"key":"ref_199","unstructured":"(2025, September 12). HIV Data and Statistics. Available online: https:\/\/www.who.int\/teams\/global-hiv-hepatitis-and-stis-programmes\/hiv\/strategic-information\/hiv-data-and-statistics."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1111\/bcp.12403","article-title":"The Evolution of Three Decades of Antiretroviral Therapy: Challenges, Triumphs and the Promise of the Future","volume":"79","author":"Tseng","year":"2015","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1080\/17512433.2019.1698946","article-title":"Beyond One Pill, Once Daily: Current Challenges of Antiretroviral Therapy Management in the United States","volume":"12","author":"Masters","year":"2019","journal-title":"Expert Rev. Clin. Pharmacol."},{"key":"ref_202","doi-asserted-by":"crossref","unstructured":"Woldegeorgis, B.Z., Asgedom, Y.S., Habte, A., Kassie, G.A., and Badacho, A.S. (2024). Highly Active Antiretroviral Therapy is Necessary but Not Sufficient. A Systematic Review and Meta-Analysis of Mortality Incidence Rates and Predictors among HIV-Infected Adults Receiving Treatment in Ethiopia, a Surrogate Study for Resource-Poor Settings. BMC Public Health, 24.","DOI":"10.1186\/s12889-024-19268-1"},{"key":"ref_203","first-page":"e202112","article-title":"Impact of Human Immunodeficiency Virus on Pulmonary Vascular Disease","volume":"2021","author":"Kumar","year":"2021","journal-title":"Glob. Cardiol. Sci. Pract."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.yjmcc.2007.09.006","article-title":"Pathogenic Mechanisms of Pulmonary Arterial Hypertension","volume":"44","author":"Chan","year":"2008","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s12981-015-0078-3","article-title":"HIV Related Pulmonary Arterial Hypertension: Epidemiology in Africa, Physiopathology, and Role of Antiretroviral Treatment","volume":"12","author":"Bigna","year":"2015","journal-title":"AIDS Res. Ther."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"e150","DOI":"10.1161\/CIRCRESAHA.124.323979","article-title":"HIV-Associated Hypertension: Risks, Mechanisms, and Knowledge Gaps","volume":"134","author":"Prakash","year":"2024","journal-title":"Circ. Res."},{"key":"ref_207","first-page":"e27390","article-title":"An Outlook on the Etiopathogenesis of Pulmonary Hypertension in HIV","volume":"14","author":"Palakeel","year":"2022","journal-title":"Cureus"},{"key":"ref_208","first-page":"12","article-title":"Pulmonary Arterial Hypertension in Human Immunodeficiency Virus Infections","volume":"12","author":"Singh","year":"2024","journal-title":"Southwest Respir. Crit. Care Chron."},{"key":"ref_209","doi-asserted-by":"crossref","unstructured":"Chandran, S., Adler, M., Chen, L., Kaur, S., and Dhillon, N.K. (2025). HIV-Tat and Vascular Endothelium: Implications in the HIV Associated Brain, Heart, and Lung Complications. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1621338"},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"C592","DOI":"10.1152\/ajpcell.00379.2025","article-title":"Role of HIV-Encoded Proteins in Cardiovascular Disease","volume":"329","author":"Kovacs","year":"2025","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_211","doi-asserted-by":"crossref","unstructured":"Anand, A.R., Rachel, G., and Parthasarathy, D. (2018). HIV Proteins and Endothelial Dysfunction: Implications in Cardiovascular Disease. Front. Cardiovasc. Med., 5.","DOI":"10.3389\/fcvm.2018.00185"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1161\/CIRCULATIONAHA.114.006978","article-title":"Human Immunodeficiency Virus\u2013Associated Pulmonary Arterial Hypertension","volume":"131","author":"Butrous","year":"2015","journal-title":"Circulation"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1086\/682222","article-title":"Prevalence and Hospital Discharge Status of Human Immunodeficiency Virus\u2013Associated Pulmonary Arterial Hypertension in the United States","volume":"5","author":"Annangi","year":"2015","journal-title":"Pulm. Circ."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"58","DOI":"10.4103\/2045-8932.109915","article-title":"Human Immunodeficiency Virus-1 Transgene Expression Increases Pulmonary Vascular Resistance and Exacerbates Hypoxia-Induced Pulmonary Hypertension Development","volume":"3","author":"Porter","year":"2013","journal-title":"Pulm. Circ."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1164\/rccm.200601-005OC","article-title":"HIV-1 Nef Is Associated with Complex Pulmonary Vascular Lesions in SHIV-Nef\u2013Infected Macaques","volume":"174","author":"Marecki","year":"2006","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_216","first-page":"174","article-title":"The Intersection of HIV and Pulmonary Vascular Health: From HIV Evolution to Vascular Cell Types to Disease Mechanisms","volume":"3","author":"Garcia","year":"2024","journal-title":"J. Vasc. Dis."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"186","DOI":"10.4254\/wjh.v10.i2.186","article-title":"Hepatitis C Virus: Morphogenesis, Infection and Therapy","volume":"10","author":"Morozov","year":"2018","journal-title":"World J. Hepatol."},{"key":"ref_218","doi-asserted-by":"crossref","unstructured":"Suhail, M., Sohrab, S.S., Kamal, M.A., and Azhar, E.I. (2022). Role of Hepatitis C Virus in Hepatocellular Carcinoma and Neurological Disorders: An Overview. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.913231"},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"676","DOI":"10.3390\/gastroent15030049","article-title":"Hepatitis C Virus: History and Current Knowledge","volume":"15","author":"Topi","year":"2024","journal-title":"Gastroenterol. Insights"},{"key":"ref_220","doi-asserted-by":"crossref","unstructured":"Mazumder, H., Hossain, M.F., Shrestha, P., Mahmud, S., Husain, M., and Ahmed, R. (2024). Prevalence and Associated Risk Factors of Current Hepatitis C Infection among U.S. General Population and Injection Drug Users Aged 20\u201359 Years: NHANES 2009\u20132018. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0309345"},{"key":"ref_221","doi-asserted-by":"crossref","unstructured":"Stroffolini, T., and Stroffolini, G. (2024). Prevalence and Modes of Transmission of Hepatitis C Virus Infection: A Historical Worldwide Review. Viruses, 16.","DOI":"10.3390\/v16071115"},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1038\/s41575-023-00759-2","article-title":"Global Epidemiology of Cirrhosis\u2014Aetiology, Trends and Predictions","volume":"20","author":"Huang","year":"2023","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1002\/lt.24973","article-title":"Decreasing Mortality and Disease Severity in Hepatitis C Patients Awaiting Liver Transplantation in the United States","volume":"24","author":"Kwong","year":"2018","journal-title":"Liver Transpl."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"e69","DOI":"10.1016\/j.chest.2015.09.018","article-title":"Severe Pulmonary Arterial Hypertension in Patients Treated for Hepatitis C With Sofosbuvir","volume":"149","author":"Renard","year":"2016","journal-title":"Chest"},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.2169\/internalmedicine.56.7822","article-title":"Interferon Therapy Exacerbated Pulmonary Hypertension in a Patient with Hepatitis C Virus Infection: Pathogenic Interplay among Multiple Risk Factors","volume":"56","author":"Tsuchiya","year":"2017","journal-title":"Intern. Med."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"S37","DOI":"10.1016\/j.aucc.2020.04.117","article-title":"A Case of Pulmonary Arterial Hypertension Secondary to Hepatitis C Direct Antiviral Treatment with Harvoni\u00ae (Ledipasvir\/Sofosbuvir Fixed-Dose Combination)","volume":"33","author":"Doherty","year":"2020","journal-title":"Aust. Crit. Care"},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1183\/09031936.00057914","article-title":"Pulmonary Arterial Hypertension in Patients Treated with Interferon","volume":"44","author":"Savale","year":"2014","journal-title":"Eur. Respir. J."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"9599","DOI":"10.1073\/pnas.171311298","article-title":"Human Hepatitis C Virus NS5A Protein Alters Intracellular Calcium Levels, Induces Oxidative Stress, and Activates STAT-3 and NF-Kappa B","volume":"98","author":"Gong","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1161\/CIRCULATIONAHA.110.963314","article-title":"Signal Transducers and Activators of Transcription-3\/Pim1 Axis Plays a Critical Role in the Pathogenesis of Human Pulmonary Arterial Hypertension","volume":"123","author":"Paulin","year":"2011","journal-title":"Circulation"},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"211","DOI":"10.3851\/IMP2733","article-title":"Analysis of Hepatitis C Viral Kinetics during Administration of Two Nucleotide Analogues: Sofosbuvir (GS-7977) and GS-0938","volume":"19","author":"Guedj","year":"2014","journal-title":"Antivir. Ther."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1080\/1040841X.2018.1501345","article-title":"Human Endogenous Retrovirus-K (HML-2): A Comprehensive Review","volume":"44","author":"Henderson","year":"2018","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"8788","DOI":"10.1128\/JVI.78.16.8788-8798.2004","article-title":"Human Endogenous Retrovirus Family HERV-K(HML-5): Status, Evolution, and Reconstruction of an Ancient Betaretrovirus in the Human Genome","volume":"78","author":"Lavie","year":"2004","journal-title":"J. Virol."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"7187","DOI":"10.1128\/JVI.00544-15","article-title":"Human Endogenous Retrovirus Type K (HERV-K) Particles Package and Transmit HERV-K\u2013Related Sequences","volume":"89","author":"Kaplan","year":"2015","journal-title":"J. Virol."},{"key":"ref_234","doi-asserted-by":"crossref","unstructured":"Simula, E.R., Jasemi, S., Cossu, D., Fais, M., Cossu, I., Chessa, V., Canu, M., and Sechi, L.A. (2025). Human Endogenous Retroviruses as Novel Therapeutic Targets in Neurodegenerative Disorders. Vaccines, 13.","DOI":"10.3390\/vaccines13040415"},{"key":"ref_235","doi-asserted-by":"crossref","unstructured":"Johanning, G.L., Malouf, G.G., Zheng, X., Esteva, F.J., Weinstein, J.N., Wang-Johanning, F., and Su, X. (2017). Expression of Human Endogenous Retrovirus-K is Strongly Associated with the Basal-like Breast Cancer Phenotype. Sci. Rep., 7.","DOI":"10.1038\/srep41960"},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"2523888","DOI":"10.1080\/21505594.2025.2523888","article-title":"The Relationship between HERVs and Exogenous Viral Infections: A Focus on the Value of HERVs in Disease Prediction and Treatment","volume":"16","author":"Dou","year":"2025","journal-title":"Virulence"},{"key":"ref_237","doi-asserted-by":"crossref","unstructured":"Mantovani, F., Kitsou, K., and Magiorkinis, G. (2024). HERVs: Expression Control Mechanisms and Interactions in Diseases and Human Immunodeficiency Virus Infection. Genes, 15.","DOI":"10.3390\/genes15020192"},{"key":"ref_238","doi-asserted-by":"crossref","unstructured":"Zhang, M., Zheng, S., and Liang, J.Q. (2022). Transcriptional and Reverse Transcriptional Regulation of Host Genes by Human Endogenous Retroviruses in Cancers. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.946296"},{"key":"ref_239","doi-asserted-by":"crossref","unstructured":"Stricker, E., Peckham-Gregory, E.C., and Scheurer, M.E. (2023). HERVs and Cancer\u2014A Comprehensive Review of the Relationship of Human Endogenous Retroviruses and Human Cancers. Biomedicines, 11.","DOI":"10.3390\/biomedicines11030936"},{"key":"ref_240","doi-asserted-by":"crossref","unstructured":"Costa, B., and Vale, N. (2023). Exploring HERV-K (HML-2) Influence in Cancer and Prospects for Therapeutic Interventions. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241914631"},{"key":"ref_241","doi-asserted-by":"crossref","unstructured":"Kozubek, P., Ku\u017aniar, J., Czaja, M., Sitka, H., Kochman, U., and Leszek, J. (2025). Human Endogenous Retroviruses and Their Putative Role in Pathogenesis of Alzheimer\u2019s Disease, Inflammation, and Senescence. Biomedicines, 13.","DOI":"10.3390\/biomedicines13010059"},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1161\/CIRCULATIONAHA.117.027589","article-title":"Upregulation of Human Endogenous Retrovirus-K is Linked to Immunity and Inflammation in Pulmonary Arterial Hypertension","volume":"136","author":"Saito","year":"2017","journal-title":"Circulation"},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"1936","DOI":"10.1161\/CIRCULATIONAHA.117.031190","article-title":"Human Endogenous Retrovirus K and Pulmonary Arterial Hypertension","volume":"136","author":"Culley","year":"2017","journal-title":"Circulation"},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"669","DOI":"10.34133\/research.0669","article-title":"Microbiome\u2013Immune Interaction in Pulmonary Arterial Hypertension: What Have We Missed?","volume":"8","author":"Zhou","year":"2025","journal-title":"Research"},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1164\/rccm.202102-0446OC","article-title":"Endogenous Retroviral Elements Generate Pathologic Neutrophils in Pulmonary Arterial Hypertension","volume":"206","author":"Taylor","year":"2022","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_246","first-page":"e146416","article-title":"Monocyte-Released HERV-K dUTPase Engages TLR4 and MCAM Causing Endothelial Mesenchymal Transition","volume":"6","author":"Otsuki","year":"2021","journal-title":"JCI Insight"},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1186\/s12931-025-03182-0","article-title":"Altered Maturation and Activation State of Circulating Monocytes is Associated with Their Enhanced Recruitment in Pulmonary Arterial Hypertension","volume":"26","author":"Harper","year":"2025","journal-title":"Respir. Res."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"e12142","DOI":"10.1002\/pul2.12142","article-title":"The Impact of COVID-19 Pandemic on Pulmonary Hypertension: What Have We Learned?","volume":"12","author":"Hinojosa","year":"2022","journal-title":"Pulm. Circ."},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1513\/AnnalsATS.202008-1014ED","article-title":"COVID-19 and Pulmonary Arterial Hypertension: Early Data and Many Questions","volume":"17","author":"Farha","year":"2020","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_250","first-page":"PA3587","article-title":"Controversies over the Impact of the COVID-19 Pandemic on Patients with Pulmonary Arterial Hypertension","volume":"58","author":"Bertici","year":"2021","journal-title":"Eur. Respir. J."},{"key":"ref_251","doi-asserted-by":"crossref","unstructured":"Tudoran, C., Tudoran, M., Lazureanu, V.E., Marinescu, A.R., Pop, G.N., Pescariu, A.S., Enache, A., and Cut, T.G. (2021). Evidence of Pulmonary Hypertension after SARS-CoV-2 Infection in Subjects without Previous Significant Cardiovascular Pathology. J. Clin. Med., 10.","DOI":"10.3390\/jcm10020199"},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s43168-022-00158-2","article-title":"Impact and Predictors of Outcome of COVID-19 in Pulmonary Hypertension Patients","volume":"16","author":"Soliman","year":"2022","journal-title":"Egypt. J. Bronchol."},{"key":"ref_253","first-page":"101053","article-title":"Pulmonary Arterial Hypertension and COVID-19: Piecing the Puzzle","volume":"84","author":"Charif","year":"2023","journal-title":"Respir. Med. Res."},{"key":"ref_254","doi-asserted-by":"crossref","unstructured":"Mamzer, A., Waligora, M., Kopec, G., Ptaszynska-Kopczynska, K., Kurzyna, M., Darocha, S., Florczyk, M., Mroczek, E., Mularek-Kubzdela, T., and Smukowska-Gorynia, A. (2022). Impact of the COVID-19 Pandemic on Pulmonary Hypertension Patients: Insights from the BNP-PL National Database. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph19148423"},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"e343","DOI":"10.5001\/omj.2022.52","article-title":"Respiratory Complications after COVID-19","volume":"37","author":"Bennji","year":"2022","journal-title":"Oman Med. J."},{"key":"ref_256","doi-asserted-by":"crossref","unstructured":"Ambardar, S.R., Hightower, S.L., Huprikar, N.A., Chung, K.K., Singhal, A., and Collen, J.F. (2021). Post-COVID-19 Pulmonary Fibrosis: Novel Sequelae of the Current Pandemic. J. Clin. Med., 10.","DOI":"10.3390\/jcm10112452"},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"101004","DOI":"10.1016\/j.cpcardiol.2021.101004","article-title":"Severe Pulmonary Hypertension: An Important Sequel After Severe Post-Acute COVID-19 Pneumonia","volume":"47","author":"Rojas","year":"2022","journal-title":"Curr. Probl. Cardiol."},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1007\/s12016-021-08848-3","article-title":"A Review of Persistent Post-COVID Syndrome (PPCS)","volume":"64","author":"Oronsky","year":"2023","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1038\/s41590-021-00937-x","article-title":"TLR2 Senses the SARS-CoV-2 Envelope Protein to Produce Inflammatory Cytokines","volume":"22","author":"Zheng","year":"2021","journal-title":"Nat. Immunol."},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"e68563","DOI":"10.7554\/eLife.68563","article-title":"SARS-CoV-2 Spike Protein Induces Inflammation via TLR2-Dependent Activation of the NF-\u03baB Pathway","volume":"10","author":"Khan","year":"2021","journal-title":"eLife"},{"key":"ref_261","doi-asserted-by":"crossref","unstructured":"Halajian, E.A., LeBlanc, E.V., Gee, K., and Colpitts, C.C. (2022). Activation of TLR4 by Viral Glycoproteins: A Double-Edged Sword?. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.1007081"},{"key":"ref_262","doi-asserted-by":"crossref","first-page":"eabl4348","DOI":"10.1126\/sciimmunol.abl4348","article-title":"X-Linked Recessive TLR7 Deficiency in ~1% of Men under 60 Years Old with Life-Threatening COVID-19","volume":"6","author":"Asano","year":"2021","journal-title":"Sci. Immunol."},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1016\/S0140-6736(20)30937-5","article-title":"Endothelial Cell Infection and Endotheliitis in COVID-19","volume":"395","author":"Varga","year":"2020","journal-title":"Lancet"},{"key":"ref_264","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1056\/NEJMoa2015432","article-title":"Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in COVID-19","volume":"383","author":"Ackermann","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_265","doi-asserted-by":"crossref","unstructured":"Ejikeme, C., and Safdar, Z. (2024). Exploring the Pathogenesis of Pulmonary Vascular Disease. Front. Med., 11.","DOI":"10.3389\/fmed.2024.1402639"},{"key":"ref_266","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.cytogfr.2021.10.003","article-title":"COVID-19 and Dys-Regulation of Pulmonary Endothelium: Implications for Vascular Remodeling","volume":"63","author":"Jadaun","year":"2022","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_267","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1159\/000518914","article-title":"Autopsy-Based Pulmonary and Vascular Pathology: Pulmonary Endotheliitis and Multi-Organ Involvement in COVID-19 Associated Deaths","volume":"101","author":"Haberecker","year":"2022","journal-title":"Respiration"},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1016\/j.ajpath.2021.04.010","article-title":"ACE2 Down-Regulation May Act as a Transient Molecular Disease Causing RAAS Dysregulation and Tissue Damage in the Microcirculatory Environment Among COVID-19 Patients","volume":"191","author":"Ramos","year":"2021","journal-title":"Am. J. Pathol."},{"key":"ref_269","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1002\/path.5471","article-title":"Angiotensin-converting Enzyme 2 (ACE2), SARS-CoV-2 and the Pathophysiology of Coronavirus Disease 2019 (COVID-19)","volume":"251","author":"Bourgonje","year":"2020","journal-title":"J. Pathol."},{"key":"ref_270","doi-asserted-by":"crossref","unstructured":"Gagliardi, S., Hotchkin, T., Tibebe, H., Hillmer, G., Marquez, D., Izumi, C., Chang, J., Diggs, A., Ezaki, J., and Suzuki, Y.J. (2025). The Renin\u2013Angiotensin System Modulates SARS-CoV-2 Entry via ACE2 Receptor. Viruses, 17.","DOI":"10.1101\/2025.06.25.661409"},{"key":"ref_271","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.thromres.2021.04.012","article-title":"COVID-19 and Thrombotic Microangiopathies","volume":"202","author":"Tiwari","year":"2021","journal-title":"Thromb. Res."},{"key":"ref_272","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1093\/ckj\/sfab024","article-title":"Successful Treatment of a COVID-19 Patient with Thrombotic Microangiopathy","volume":"14","author":"Safak","year":"2021","journal-title":"Clin. Kidney J."},{"key":"ref_273","first-page":"103963","article-title":"COVID-19 Microangiopathy: Insights into plasma exchange as a therapeutic strategy","volume":"47","author":"Baykara","year":"2025","journal-title":"Rev. Bras. Hematol. Hemoter."},{"key":"ref_274","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1007\/s10456-021-09805-6","article-title":"COVID-19 is a Systemic Vascular Hemopathy: Insight for Mechanistic and Clinical Aspects","volume":"24","author":"Smadja","year":"2021","journal-title":"Angiogenesis"},{"key":"ref_275","doi-asserted-by":"crossref","unstructured":"Chen, P.-Y., Schwartz, M.A., and Simons, M. (2020). Endothelial-to-Mesenchymal Transition, Vascular Inflammation, and Atherosclerosis. Front. Cardiovasc. Med., 7.","DOI":"10.3389\/fcvm.2020.00053"},{"key":"ref_276","doi-asserted-by":"crossref","unstructured":"Zhang, L., Tang, C., Zhang, M., Tong, X., Xie, Y., Yan, R., Wang, X., Zhang, X., Liu, D., and Li, S. (2022). Single Cell Meta-Analysis of EndMT and EMT State in COVID-19. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.976512"},{"key":"ref_277","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1186\/s12964-024-01665-z","article-title":"Diverse Roles of SARS-CoV-2 Spike and Nucleocapsid Proteins in EndMT Stimulation through the TGF-\u03b2-MRTF Axis Inhibited by Aspirin","volume":"22","author":"Ciszewski","year":"2024","journal-title":"Cell Commun. Signal"},{"key":"ref_278","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s00441-024-03900-y","article-title":"SARS-CoV-2-Related Peptides Induce Endothelial-to-Mesenchymal Transition in Endothelial Capillary Cells Derived from Different Body Districts: Focus on Membrane (M) Protein","volume":"397","author":"Baldassarro","year":"2024","journal-title":"Cell Tissue Res."},{"key":"ref_279","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s41232-023-00259-5","article-title":"Innate Immune Recognition against SARS-CoV-2","volume":"43","author":"Yamada","year":"2023","journal-title":"Inflamm. Regen."},{"key":"ref_280","doi-asserted-by":"crossref","first-page":"5077","DOI":"10.2147\/JIR.S474707","article-title":"Interplay of TLR4 and SARS-CoV-2: Unveiling the Complex Mechanisms of Inflammation and Severity in COVID-19 Infections","volume":"17","author":"Asaba","year":"2024","journal-title":"JIR"},{"key":"ref_281","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1038\/s41401-022-00998-0","article-title":"Endothelial Dysfunction in COVID-19: An Overview of Evidence, Biomarkers, Mechanisms and Potential Therapies","volume":"44","author":"Xu","year":"2023","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_282","doi-asserted-by":"crossref","first-page":"101070","DOI":"10.1016\/j.jacadv.2024.101070","article-title":"Clinical Implications of COVID-19-Related Endothelial Dysfunction","volume":"3","author":"Aljadah","year":"2024","journal-title":"JACC Adv."},{"key":"ref_283","doi-asserted-by":"crossref","unstructured":"Oliveira, R.K.F., Nyasulu, P.S., Iqbal, A.A., Hamdan Gul, M., Ferreira, E.V.M., Leclair, J.W., Htun, Z.M., Howard, L.S., Mocumbi, A.O., and Bryant, A.J. (2022). Cardiopulmonary Disease as Sequelae of Long-Term COVID-19: Current Perspectives and Challenges. Front. Med., 9.","DOI":"10.3389\/fmed.2022.1041236"},{"key":"ref_284","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.1016\/j.rmed.2013.09.017","article-title":"Pulmonary Hypertension in Obesity-Hypoventilation Syndrome","volume":"107","author":"Kauppert","year":"2013","journal-title":"Respir. Med."},{"key":"ref_285","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1164\/rccm.202112-2761OC","article-title":"COVID-19 in Patients with Pulmonary Hypertension: A National Prospective Cohort Study","volume":"206","author":"Montani","year":"2022","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_286","doi-asserted-by":"crossref","unstructured":"Riou, M., Coste, F., Meyer, A., Enache, I., Talha, S., Charloux, A., Reboul, C., and Geny, B. (2024). Mechanisms of Pulmonary Vasculopathy in Acute and Long-Term COVID-19: A Review. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25094941"},{"key":"ref_287","doi-asserted-by":"crossref","unstructured":"Eroume, \u00c0. (2022). Egom, E.; Shiwani, H.A.; Nouthe, B. From Acute SARS-CoV-2 Infection to Pulmonary Hypertension. Front. Physiol., 13.","DOI":"10.3389\/fphys.2022.1023758"},{"key":"ref_288","doi-asserted-by":"crossref","first-page":"723","DOI":"10.33963\/KP.a2022.0141","article-title":"An Expert Opinion of the Polish Cardiac Society Working Group on Pulmonary Circulation on Screening for Chronic Thromboembolic Pulmonary Hypertension Patients after Acute Pulmonary Embolism: Update","volume":"80","author":"Kurzyna","year":"2022","journal-title":"Pol. Heart J."},{"key":"ref_289","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s43168-023-00201-w","article-title":"Study of Pulmonary Hypertension in Post-COVID-19 Patients by Transthoracic Echocardiography","volume":"17","author":"Taha","year":"2023","journal-title":"Egypt. J. Bronchol."},{"key":"ref_290","doi-asserted-by":"crossref","unstructured":"Puk, O., Nowacka, A., Smulewicz, K., Mocna, K., Bursiewicz, W., K\u0119sy, N., Kwiecie\u0144, J., and Wici\u0144ski, M. (2022). Pulmonary Artery Targeted Therapy in Treatment of COVID-19 Related ARDS. Literature Review. Biomed. Pharmacother., 146.","DOI":"10.1016\/j.biopha.2021.112592"},{"key":"ref_291","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/j.healun.2020.04.007","article-title":"Endothelin Receptor Antagonists for Pulmonary Arterial Hypertension and COVID-19: Friend or Foe?","volume":"39","author":"Badagliacca","year":"2020","journal-title":"J. Heart Lung Transplant."},{"key":"ref_292","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.recesp.2020.05.028","article-title":"Clinical Course of COVID-19 in Pulmonary Arterial Hypertension Patients","volume":"73","author":"Nuche","year":"2020","journal-title":"Rev. Espa\u00f1ola Cardiol."},{"key":"ref_293","first-page":"7","article-title":"Diagnosis and Treatment of Pulmonary Hypertension\u2014Based on the 2022 ESC Guidelines","volume":"9","year":"2023","journal-title":"Lek. POZ"},{"key":"ref_294","doi-asserted-by":"crossref","first-page":"3618","DOI":"10.1093\/eurheartj\/ehac237","article-title":"2022 ESC\/ERS Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension: Developed by the Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS). Endorsed by the International Society for Heart and Lung Transplantation (ISHLT) and the European Reference Network on Rare Respiratory Diseases (ERN-LUNG)","volume":"43","author":"Humbert","year":"2022","journal-title":"Eur. Heart J."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/22\/11143\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T05:13:51Z","timestamp":1763615631000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/22\/11143"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,18]]},"references-count":294,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["ijms262211143"],"URL":"https:\/\/doi.org\/10.3390\/ijms262211143","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,18]]}}}