{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T00:33:47Z","timestamp":1794011627226,"version":"4.8.0"},"reference-count":162,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011698","name":"Junta de Comunidades de Castilla-La Mancha, Spain","doi-asserted-by":"publisher","award":["SBPLY\/23\/180225\/000081"],"award-info":[{"award-number":["SBPLY\/23\/180225\/000081"]}],"id":[{"id":"10.13039\/501100011698","id-type":"DOI","asserted-by":"publisher"}]},{"name":"I+D Biomedicine Activities Program 2022","award":["P2022\/BMD-7223 CIFRA_COR_CM"],"award-info":[{"award-number":["P2022\/BMD-7223 CIFRA_COR_CM"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Calcific aortic valve disease (CAVD) is a progressive disorder where molecular alterations occur long before visible calcification, making early biomarkers essential. Extracellular vesicles (EVs) have gained attention as stable biomarkers due to their lipid bilayer, which protects proteins, lipids, and RNAs, ensuring reliable detection even in archived samples. This review highlights the role of EVs as biomarkers and delivery tools in CAVD. EVs derived from valvular endothelial, interstitial, and immune cells carry disease-specific signatures, including osteogenic proteins (BMP-2, Annexins), inflammatory miRNAs (miR-30b, miR-122-5p), and lipid mediators. These reflect early pathogenic processes before macroscopic calcification develops. Their presence in minimally invasive samples such as blood, urine, or saliva facilitates diagnosis, while their stability supports long-term monitoring of disease progression and therapeutic response. Advances in purification and single-EV analysis increase specificity, though challenges remain in standardizing methods and distinguishing CAVD-derived EVs from those in atherosclerosis. Beyond diagnostics, engineered EVs show promise as therapeutic carriers. Delivery of anti-calcific miRNAs or combined RNA cargos has reduced calcification and inflammation in preclinical models. Overall, EVs act as molecular mirrors of CAVD, enabling early diagnosis, risk stratification, and novel therapeutic strategies. Yet, clinical translation requires technical refinement and validation of the disease-specific signatures.<\/jats:p>","DOI":"10.3390\/biom15111548","type":"journal-article","created":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T11:11:16Z","timestamp":1762254676000},"page":"1548","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Extracellular Vesicles in Calcific Aortic Valve Disease: From Biomarkers to Drug Delivery Applications"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1770-2386","authenticated-orcid":false,"given":"Alberto","family":"Cook-Calvete","sequence":"first","affiliation":[{"name":"Department of Systems Biology, Faculty of Medicine, Universidad de Alcal\u00e1, 28871 Alcal\u00e1 de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3078-7321","authenticated-orcid":false,"given":"Maria","family":"Delgado-Marin","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, Faculty of Medicine, Universidad de Alcal\u00e1, 28871 Alcal\u00e1 de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4839-9143","authenticated-orcid":false,"given":"Blanca","family":"Fernandez-Rodriguez","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, Faculty of Medicine, Universidad de Alcal\u00e1, 28871 Alcal\u00e1 de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1706-8592","authenticated-orcid":false,"given":"Carlos","family":"Zaragoza","sequence":"additional","affiliation":[{"name":"Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), 28034 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n en Red de Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain"},{"name":"Unidad Mixta de Investigaci\u00f3n Cardiovascular, Departamento de Cardiolog\u00eda, Universidad Francisco de Vitoria, Pozuelo de Alarc\u00f3n, 28223 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3977-6581","authenticated-orcid":false,"given":"Marta","family":"Saura","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, Faculty of Medicine, Universidad de Alcal\u00e1, 28871 Alcal\u00e1 de Henares, Spain"},{"name":"Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), 28034 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n en Red de Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1093\/eurheartj\/ehae829","article-title":"Calcific aortic stenosis: Omics-based target discovery and therapy development","volume":"46","author":"Blaser","year":"2025","journal-title":"Eur. Heart J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1093\/icvts\/ivz268","article-title":"Life expectancy of patients undergoing surgical aortic valve replacement compared with that of the general population","volume":"30","author":"Diaz","year":"2020","journal-title":"Interact. Cardiovasc. Thorac. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ragni, E. (2025). Extracellular Vesicles: Recent Advances and Perspectives. Front. Biosci., 30.","DOI":"10.31083\/FBL36405"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1161\/CIRCULATIONAHA.122.063402","article-title":"Multiomics of Tissue Extracellular Vesicles Identifies Unique Modulators of Atherosclerosis and Calcific Aortic Valve Stenosis","volume":"148","author":"Blaser","year":"2023","journal-title":"Circulation"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Di Vito, A., Donato, A., Presta, I., Mancuso, T., Brunetti, F.S., Mastroroberto, P., Amorosi, A., Malara, N., and Donato, G. (2021). Extracellular Matrix in Calcific Aortic Valve Disease: Architecture, Dynamic and Perspectives. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22020913"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"149117","DOI":"10.1016\/j.gene.2024.149117","article-title":"Non-coding RNAs mediating the regulation of genes and signaling pathways in aortic valve calcification","volume":"936","author":"Sivan","year":"2025","journal-title":"Gene"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1016\/j.jtcvs.2013.05.011","article-title":"MicroRNA-30b is a multifunctional regulator of aortic valve interstitial cells","volume":"147","author":"Zhang","year":"2014","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Martin, P.J., Haren, N., Ghali, O., Clabaut, A., Chauveau, C., Hardouin, P., and Broux, O. (2015). Adipogenic RNAs are transferred in osteoblasts via bone marrow adipocytes-derived extracellular vesicles (EVs). BMC Cell Biol., 16.","DOI":"10.1186\/s12860-015-0057-5"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Zhang, F., Cheng, N., Han, Y., Zhang, C., and Zhang, H. (2021). miRNA Expression Profiling Uncovers a Role of miR-139-5p in Regulating the Calcification of Human Aortic Valve Interstitial Cells. Front. Genet., 12.","DOI":"10.3389\/fgene.2021.722564"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.freeradbiomed.2025.07.042","article-title":"Valvular oxidized phospholipids correlate with severity of human aortic valvular stenosis","volume":"239","author":"Resch","year":"2025","journal-title":"Free Radic. Biol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1080\/15384101.2018.1509636","article-title":"TLR-4\/microRNA-125a\/NF-\u03baB signaling modulates the immune response to Mycobacterium tuberculosis infection","volume":"17","author":"Niu","year":"2018","journal-title":"Cell Cycle"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Moreno, A., Alarc\u00f3n-Zapata, P., Guzm\u00e1n-G\u00fatierrez, E., Radojkovic, C., Contreras, H., Nova-Lampeti, E., A Z\u00fa\u00f1iga, F., Rodriguez-Alv\u00e1rez, L., Escudero, C., and Lagos, P. (2024). Changes in the Release of Endothelial Extracellular Vesicles CD144+, CCR6+, and CXCR3+ in Individuals with Acute Myocardial Infarction. Biomedicines, 12.","DOI":"10.20944\/preprints202407.1050.v1"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Ji, J., He, Q., Xia, Y., Sha, X., Liang, Q., Xu, Y., Chen, P., Dong, C., Zhao, R., and Yang, J. (2024). Circulating plasma derived exosomes from systemic lupus erythematosus aggravate lupus nephritis through miR-122-5p\/FOXO3-mediated macrophage activation. J. Nanobiotechnol., 22.","DOI":"10.1186\/s12951-024-03063-6"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"111853","DOI":"10.1016\/j.intimp.2024.111853","article-title":"Ischemia and reperfusion-injured liver-derived exosomes elicit acute lung injury through miR-122-5p regulated alveolar macrophage polarization","volume":"131","author":"Lyu","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_15","first-page":"42","article-title":"Extracellular vesicle-derived microRNA biomarkers: Goals and pitfalls. Trillium Exctracell","volume":"2","author":"Hermann","year":"2020","journal-title":"Vesicles"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Bern\u00e1th-Nagy, D., Kalinyaprak, M.S., Giannitsis, E., \u00c1brah\u00e1m, P., Leuschner, F., Frey, N., and Krohn, J.B. (2024). Circulating extracellular vesicles as biomarkers in the diagnosis, prognosis and therapy of cardiovascular diseases. Front. Cardiovasc. Med., 11.","DOI":"10.3389\/fcvm.2024.1425159"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Li, X., Li, X., Tong, L., Hu, L., Hong, Y., Zhou, R., Li, Z., Dong, M., Hou, J., and Xu, T. (2025). Systematic Evaluation of Isolation Techniques and Freeze-Thaw Effects on Plasma Extracellular Vesicle Heterogeneity and Subpopulation Profiling. J. Extracell. Biol., 4.","DOI":"10.1002\/jex2.70058"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Newman, L., and Rowland, A. (2025). Detection and Isolation of Tissue-Specific Extracellular Vesicles From the Blood. J. Extracell. Biol., 4.","DOI":"10.1002\/jex2.70059"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1161\/CIRCRESAHA.120.317979","article-title":"Multi-Omics Approaches to Define Calcific Aortic Valve Disease Pathogenesis","volume":"128","author":"Blaser","year":"2021","journal-title":"Circ. Res."},{"key":"ref_20","first-page":"28","article-title":"Endothelial ILK induces cardioprotection by preventing coronary microvascular dysfunction and endothelial-to-mesenchymal transition. Basic Res","volume":"118","author":"Reventun","year":"2023","journal-title":"Cardiol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Viegas, C., Carreira, J., Maia, T.M., Macedo, A.L., Matos, A.P., Neves, J., and Simes, D. (2024). Gla Rich Protein (GRP) Mediates Vascular Smooth Muscle Cell (VSMC) Osteogenic Differentiation, Extracellular Vesicle (EV) Calcification Propensity, and Immunomodulatory Properties. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252212406"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e12238","DOI":"10.1002\/jev2.12238","article-title":"Identification of storage conditions stabilizing extracellular vesicles preparations","volume":"11","author":"Corso","year":"2022","journal-title":"J. Extracell. Vesicles."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1021\/acsnano.0c08947","article-title":"Mesenchymal Stem Cell-Derived Extracellular Vesicles Attenuate Mitochondrial Damage and Inflammation by Stabilizing Mitochondrial DNA","volume":"15","author":"Zhao","year":"2021","journal-title":"ACS Nano"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Vago, R., Radano, G., Zocco, D., and Zarovni, N. (2022). Urine stabilization and normalization strategies favor unbiased analysis of urinary EV content. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-22577-3"},{"key":"ref_25","first-page":"251","article-title":"Extracellular vesicles: Function, resilience, biomarker, bioengineering, and clinical implications. Tzu Chi Med","volume":"36","author":"Sun","year":"2024","journal-title":"J."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Kumari, S., Lausted, C., Scherler, K., Ng, A.H.C., Lu, Y., Lee, I., Hood, L., and Wang, K. (2024). Approaches and Challenges in Characterizing the Molecular Content of Extracellular Vesicles for Biomarker Discovery. Biomolecules, 14.","DOI":"10.3390\/biom14121599"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ghadami, S., and Dellinger, K. (2023). The lipid composition of extracellular vesicles: Applications in diagnostics and therapeutic delivery. Front. Mol. Biosci., 10.","DOI":"10.3389\/fmolb.2023.1198044"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Phan, T.H., and Reed, J.H. (2024). Extracellular vesicles as next-generation therapeutics and biomarkers in amyloidosis: A new frontier. Front. Biomater. Sci., 2.","DOI":"10.3389\/fbiom.2023.1343658"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.addr.2020.03.002","article-title":"An emerging focus on lipids in extracellular vesicles","volume":"159","author":"Skotland","year":"2020","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Tanase, D.M., Valasciuc, E., Gosav, E.M., Floria, M., Costea, C.F., Dima, N., Tudorancea, I., Maranduca, M.A., and Serban, I.L. (2022). Contribution of Oxidative Stress (OS) in Calcific Aortic Valve Disease (CAVD): From Pathophysiology to Therapeutic Targets. Cells, 11.","DOI":"10.3390\/cells11172663"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Fu, E., Pan, K., and Li, Z. (2024). Engineering extracellular vesicles for targeted therapeutics in cardiovascular disease. Front. Cardiovasc. Med., 11.","DOI":"10.3389\/fcvm.2024.1503830"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"S\u00e1nchez-Esteban, S., Castro-Pinto, M., Cook-Calvete, A., Revent\u00fan, P., Delgado-Mar\u00edn, M., Benito-Manzanaro, L., Hernandez, I., L\u00f3pez-Menendez, J., Zamorano, J.L., and Zaragoza, C. (2022). Integrin-Linked Kinase Expression in Human Valve Endothelial Cells Plays a Protective Role in Calcific Aortic Valve Disease. Antioxidants, 11.","DOI":"10.3390\/antiox11091736"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3935","DOI":"10.1002\/ehf2.13460","article-title":"Telocytes-derived extracellular vesicles alleviate aortic valve calcification by carrying miR-30b","volume":"8","author":"Yang","year":"2021","journal-title":"ESC Heart Fail."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.jtos.2023.03.002","article-title":"MicroRNAs of extracellular vesicles derived from mesenchymal stromal cells alleviate inflammation in dry eye disease by targeting the IRAK1\/TAB2\/NF-\u03baB pathway","volume":"28","author":"Wang","year":"2023","journal-title":"Ocul. Surf."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.cmet.2019.07.011","article-title":"Extracellular miRNAs: From Biomarkers to Mediators of Physiology and Disease","volume":"30","author":"Mori","year":"2019","journal-title":"Cell Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.pharmthera.2017.02.020","article-title":"Exosomes: Therapy delivery tools and biomarkers of diseases","volume":"174","author":"Barile","year":"2017","journal-title":"Pharmacol. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"100635","DOI":"10.1016\/j.clinsp.2025.100635","article-title":"Extracellular vesicles as cancer biomarkers and drug delivery strategies in clinical settings: Advances, perspectives, and challenges","volume":"80","author":"Santos","year":"2025","journal-title":"Clinics"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"555","DOI":"10.7705\/biomedica.5749","article-title":"Retos y oportunidades en el estudio de ves\u00edculas extracelulares: Contexto institucional a nivel mundial y situaci\u00f3n actual en Colombia","volume":"41","year":"2021","journal-title":"Biom\u00e9dica"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Zhang, X., Wu, Y., Cheng, Q., Bai, L., Huang, S., and Gao, J. (2022). Extracellular Vesicles in Cardiovascular Diseases: Diagnosis and Therapy. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.875376"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1535750","DOI":"10.1080\/20013078.2018.1535750","article-title":"Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines","volume":"7","author":"Witwer","year":"2018","journal-title":"J. Extracell. Vesicles"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e12385","DOI":"10.1002\/jev2.12385","article-title":"MIBlood-EV: Minimal information to enhance the quality and reproducibility of blood extracellular vesicle research","volume":"12","author":"Lucien","year":"2023","journal-title":"J. Extracell. Vesicles"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Jin, Y., Chen, K., Wang, Z., Wang, Y., Liu, J., Lin, L., Shao, Y., Gao, L., Yin, H., and Cui, C. (2016). DNA in serum extracellular vesicles is stable under different storage conditions. BMC Cancer, 16.","DOI":"10.1186\/s12885-016-2783-2"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1568","DOI":"10.3390\/molecules19021568","article-title":"miRNA in Plasma Exosome is Stable under Different Storage Conditions","volume":"19","author":"Ge","year":"2014","journal-title":"Molecules"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"113872","DOI":"10.1016\/j.addr.2021.113872","article-title":"Adherence to minimal experimental requirements for defining extracellular vesicles and their functions","volume":"176","author":"Poupardin","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1124\/pharmrev.122.000788","article-title":"Emergence of Extracellular Vesicles as \u201cLiquid Biopsy\u201d for Neurological Disorders: Boom or Bust","volume":"76","author":"Kumar","year":"2024","journal-title":"Pharmacol. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Ma, C., Ding, R., Hao, K., Du, W., Xu, L., Gao, Q., and Yu, C. (2023). Storage Stability of Blood Samples for miRNAs in Glycosylated Extracellular Vesicles. Molecules, 29.","DOI":"10.3390\/molecules29010103"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Li, X., Dai, Y., Han, Y., Wei, X., Wei, G., Chen, W., Kong, S., He, Y., and Liu, H. (2024). Neutrophil N1 polarization induced by cardiomyocyte-derived extracellular vesicle miR-9-5p aggravates myocardial ischemia\/reperfusion injury. J. Nanobiotechnol., 22.","DOI":"10.1186\/s12951-024-02902-w"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2202964","DOI":"10.1002\/advs.202202964","article-title":"M2 Macrophage-Derived sEV Regulate Pro-Inflammatory CCR2 + Macrophage Subpopulations to Favor Post-AMI Cardiac Repair","volume":"10","author":"Li","year":"2023","journal-title":"Adv. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Dang, G., Li, T., Yang, D., Yang, G., Du, X., Yang, J., Miao, Y., Han, L., Ma, X., and Song, Y. (2022). T lymphocyte-derived extracellular vesicles aggravate abdominal aortic aneurysm by promoting macrophage lipid peroxidation and migration via pyruvate kinase muscle isozyme 2. Redox Biol., 50.","DOI":"10.1016\/j.redox.2022.102257"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Saxena, S., Volpe, M.C., Agostinis, C., Vodret, S., Ring, N.A.R., Colliva, A., Vuerich, R., Braga, L., Cook-Calvete, A., and Romano, F. (2025). Anti-miRNA therapeutics for uterine fibroids. Biomed. Pharmacother., 185.","DOI":"10.1016\/j.biopha.2025.117946"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"217352","DOI":"10.1016\/j.canlet.2024.217352","article-title":"Protein profile in urinary extracellular vesicles is a marker of malignancy and correlates with muscle invasiveness in urinary bladder cancer","volume":"609","author":"Steiner","year":"2025","journal-title":"Cancer Lett."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.jhep.2023.02.027","article-title":"Liquid biopsy-based protein biomarkers for risk prediction, early diagnosis, and prognostication of cholangiocarcinoma","volume":"79","author":"Lapitz","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"22793","DOI":"10.1021\/acsnano.4c08486","article-title":"Advances in Extracellular-Vesicles-Based Diagnostic and Therapeutic Approaches for Ocular Diseases","volume":"18","author":"Su","year":"2024","journal-title":"ACS Nano"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Krohn, J.B., Aikawa, E., Aikawa, M., Hutcheson, J.D., Sahoo, S., and Fish, J.E. (2022). Editorial: Extracellular vesicles in cardiovascular inflammation and calcification. Front. Cardiovasc. Med., 9.","DOI":"10.3389\/fcvm.2022.1077124"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/s41580-022-00460-3","article-title":"Challenges and directions in studying cell\u2013cell communication by extracellular vesicles","volume":"23","author":"Carter","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e12404","DOI":"10.1002\/jev2.12404","article-title":"Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches","volume":"13","author":"Welsh","year":"2024","journal-title":"J. Extracell. Vesicles"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Singh, M., Tiwari, P.K., Kashyap, V., and Kumar, S. (2025). Proteomics of Extracellular Vesicles: Recent Updates, Challenges and Limitations. Proteomes, 13.","DOI":"10.3390\/proteomes13010012"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1007\/s00018-019-03071-y","article-title":"Extracellular vesicle isolation methods: Rising impact of size-exclusion chromatography","volume":"76","author":"Roura","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_59","first-page":"80","article-title":"Isolation and analysis methods of extracellular vesicles (EVs). Extracell. Vesicles Circ","volume":"2","author":"Zhao","year":"2021","journal-title":"Nucl. Acids"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1080\/10717544.2021.1951896","article-title":"Preserving extracellular vesicles for biomedical applications: Consideration of storage stability before and after isolation","volume":"28","author":"Yuan","year":"2021","journal-title":"Drug Deliv."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Xu, D., Di, K., Fan, B., Wu, J., Gu, X., Sun, Y., Khan, A., Li, P., and Li, Z. (2022). MicroRNAs in extracellular vesicles: Sorting mechanisms, diagnostic value, isolation, and detection technology. Front. Bioeng. Biotechnol., 10.","DOI":"10.3389\/fbioe.2022.948959"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1038\/s41467-023-36932-z","article-title":"Multiplexed analysis of EV reveals specific biomarker composition with diagnostic impact","volume":"14","author":"Spitzberg","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e12200","DOI":"10.1002\/jev2.12200","article-title":"Lipid-based strategies used to identify extracellular vesicles in flow cytometry can be confounded by lipoproteins: Evaluations of annexin V, lactadherin, and detergent lysis","volume":"11","author":"Botha","year":"2022","journal-title":"J. Extracell. Vesicles"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Ciferri, M.C., Quarto, R., and Tasso, R. (2021). Extracellular Vesicles as Biomarkers and Therapeutic Tools: From Pre-Clinical to Clinical Applications. Biology, 10.","DOI":"10.3390\/biology10050359"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2895","DOI":"10.1113\/JP271338","article-title":"Extracellular vesicles in cardiovascular calcification: Expanding current paradigms","volume":"594","author":"Krohn","year":"2016","journal-title":"J. Physiol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Tandon, I., Quinn, K.P., and Balachandran, K. (2021). Label-Free Multiphoton Microscopy for the Detection and Monitoring of Calcific Aortic Valve Disease. Front. Cardiovasc. Med., 8.","DOI":"10.3389\/fcvm.2021.688513"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Veziroglu, E.M., and Mias, G.I. (2020). Characterizing Extracellular Vesicles and Their Diverse RNA Contents. Front. Genet., 11.","DOI":"10.3389\/fgene.2020.00700"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1160\/TH07-05-0334","article-title":"Increased levels of circulating microparticles in patients with severe aortic valve stenosis","volume":"99","author":"Diehl","year":"2008","journal-title":"Thromb. Haemost."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Lorite, P., Dom\u00ednguez, J.N., Palomeque, T., and Torres, M.I. (2024). Extracellular Vesicles: Advanced Tools for Disease Diagnosis, Monitoring, and Therapies. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26010189"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Hulanicka, M., Garncarz, M., Parzeniecka-Jaworska, M., and Jank, M. (2014). Plasma miRNAs as potential biomarkers of chronic degenerative valvular disease in Dachshunds. BMC Vet. Res., 10.","DOI":"10.1186\/s12917-014-0205-8"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/j.jacbts.2022.05.002","article-title":"Plasminogen Activator Inhibitor-1\u2013Positive Platelet-Derived Extracellular Vesicles Predicts MACE and the Proinflammatory SMC Phenotype","volume":"7","author":"Jung","year":"2022","journal-title":"JACC Basic Transl. Sci."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Verwer, M.C., Mekke, J., Timmerman, N., Waissi, F., Boltjes, A., Pasterkamp, G., de Borst, G.J., and de Kleijn, D.P.V. (2023). Comparison of cardiovascular biomarker expression in extracellular vesicles, plasma and carotid plaque for the prediction of MACE in CEA patients. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-27916-6"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Xiao, Y., Liang, J., Witwer, K.W., Zhang, Y., Wang, Q., and Yin, H. (2022). Extracellular vesicle-associated microRNA-30b-5p activates macrophages through the SIRT1\/ NF-\u03baB pathway in cell senescence. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.955175"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/s41378-025-00916-4","article-title":"Extracellular vesicle-based point-of-care testing for diagnosis and monitoring of Alzheimer\u2019s disease","volume":"11","author":"Li","year":"2025","journal-title":"Microsyst. Nanoeng."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Siavashy, S., Soltani, M., Rahimi, S., Hosseinali, M., Guilandokht, Z., and Raahemifar, K. (2024). Recent advancements in microfluidic-based biosensors for detection of genes and proteins: Applications and techniques. Biosens. Bioelectron. X, 19.","DOI":"10.1016\/j.biosx.2024.100489"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"165","DOI":"10.20517\/evcna.2023.72","article-title":"Electrochemical detection of extracellular vesicles for early diagnosis: A focus on disease biomarker analysis","volume":"5","author":"Zheng","year":"2024","journal-title":"Extracell. Vesicles Circ. Nucl. Acids"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Chen, J., Zheng, M., Xiao, Q., Wang, H., Chi, C., Lin, T., Wang, Y., Yi, X., and Zhu, L. (2024). Recent Advances in Microfluidic-Based Extracellular Vesicle Analysis. Micromachines, 15.","DOI":"10.20944\/preprints202403.0735.v1"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1093\/infdis\/jiw449","article-title":"MicroRNA-125b Prevents Cardiac Dysfunction in Polymicrobial Sepsis by Targeting TRAF6-Mediated Nuclear Factor \u03baB Activation and p53-Mediated Apoptotic Signaling","volume":"214","author":"Ma","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Jiang, W., Kong, L., Ni, Q., Lu, Y., Ding, W., Liu, G., Pu, L., Tang, W., and Kong, L. (2014). miR-146a Ameliorates Liver Ischemia\/Reperfusion Injury by Suppressing IRAK1 and TRAF6. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0101530"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.intimp.2018.12.043","article-title":"Extracellular vesicles containing miR-146a attenuate experimental colitis by targeting TRAF6 and IRAK1","volume":"68","author":"Wu","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/j.omtn.2020.10.016","article-title":"miR-214 Attenuates Aortic Valve Calcification by Regulating Osteogenic Differentiation of Valvular Interstitial Cells","volume":"22","author":"Li","year":"2020","journal-title":"Mol. Ther. Nucl. Acids"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1007\/s10439-019-02206-3","article-title":"miR-214 is Stretch-Sensitive in Aortic Valve and Inhibits Aortic Valve Calcification","volume":"47","author":"Salim","year":"2019","journal-title":"Ann. Biomed. Eng."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.1161\/CIRCULATIONAHA.122.060258","article-title":"Circulating MicroRNA-122-5p Is Associated with a Lack of Improvement in Left Ventricular Function After Transcatheter Aortic Valve Replacement and Regulates Viability of Cardiomyocytes Through Extracellular Vesicles","volume":"146","author":"Hosen","year":"2022","journal-title":"Circulation"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1042\/CS20130538","article-title":"microRNA-122 down-regulation may play a role in severe myocardial fibrosis in human aortic stenosis through TGF-\u03b21 up-regulation","volume":"126","author":"Beaumont","year":"2014","journal-title":"Clin. Sci."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Zhang, L., Cheng, H., Yue, Y., Li, S., Zhang, D., and He, R. (2018). H19 knockdown suppresses proliferation and induces apoptosis by regulating miR-148b\/WNT\/\u03b2-catenin in ox-LDL -stimulated vascular smooth muscle cells. J. Biomed. Sci., 25.","DOI":"10.1186\/s12929-018-0418-4"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Yu, F., Duan, Y., Liu, C., Huang, H., Xiao, X., and He, Z. (2023). Extracellular vesicles in atherosclerosis and vascular calcification: The versatile non-coding RNAs from endothelial cells and vascular smooth muscle cells. Front. Med., 10.","DOI":"10.3389\/fmed.2023.1193660"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/s42452-025-06888-4","article-title":"miR-21 in cardiovascular disease: New insights and emerging therapeutic potential","volume":"7","author":"Mollajan","year":"2025","journal-title":"Discov. Appl. Sci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1161\/HYPERTENSIONAHA.117.10094","article-title":"MicroRNA-221\/222 Family Counteracts Myocardial Fibrosis in Pressure Overload\u2013Induced Heart Failure","volume":"71","author":"Verjans","year":"2018","journal-title":"Hypertension"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"145987","DOI":"10.1016\/j.gene.2021.145987","article-title":"Exploring potential genes and pathways related to calcific aortic valve disease","volume":"808","author":"Qiao","year":"2022","journal-title":"Gene"},{"key":"ref_90","first-page":"429","article-title":"Inhibition of miR 155 5p attenuates the valvular damage induced by rheumatic heart disease","volume":"45","author":"Chen","year":"2019","journal-title":"Int. J. Mol. Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1111\/nyas.14974","article-title":"Exosomes, microvesicles, and other extracellular vesicles\u2014A Keystone Symposia report","volume":"1523","author":"Cable","year":"2023","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"6473","DOI":"10.1007\/s00210-024-03762-9","article-title":"Exosome: An overview on enhanced biogenesis by small molecules","volume":"398","author":"Bavafa","year":"2025","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1083\/jcb.201211138","article-title":"Extracellular vesicles: Exosomes, microvesicles, and friends","volume":"200","author":"Raposo","year":"2013","journal-title":"J. Cell Biol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"461","DOI":"10.4070\/kcj.2025.0022","article-title":"Exosome-Based Therapy in Cardiovascular Diseases: A New Frontier in Cardiovascular Disease Treatment","volume":"55","author":"Chae","year":"2025","journal-title":"Korean Circ. J."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Ramasubramanian, L., Du, S., Gidda, S., Bahatyrevich, N., Hao, D., Kumar, P., and Wang, A. (2022). Bioengineering Extracellular Vesicles for the Treatment of Cardiovascular Diseases. Adv. Biol., 6.","DOI":"10.1002\/adbi.202200087"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s11886-018-0968-9","article-title":"Calcific Aortic Valve Disease: A Developmental Biology Perspective","volume":"20","author":"Dutta","year":"2018","journal-title":"Curr. Cardiol. Rep."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Wang, Y., Ma, W.Q., Zhu, Y., Han, X.Q., and Liu, N. (2018). Exosomes Derived from Mesenchymal Stromal Cells Pretreated with Advanced Glycation End Product-Bovine Serum Albumin Inhibit Calcification of Vascular Smooth Muscle Cells. Front. Endocrinol., 9.","DOI":"10.3389\/fendo.2018.00524"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.biomaterials.2019.01.016","article-title":"Mesenchymal stem cell-derived extracellular vesicles and retinal ischemia-reperfusion","volume":"197","author":"Mathew","year":"2019","journal-title":"Biomaterials"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Nannan, L., Decombis, S., Terryn, C., Audonnet, S., Michel, J., Brassart-Pasco, S., Gsell, W., Himmelreich, U., and Brassart, B. (2024). Dysregulation of intercellular communication in vitro and in vivo via extracellular vesicles secreted by pancreatic duct adenocarcinoma cells and generated under the influence of the AG9 elastin peptide-conditioned microenvironment. J. Extracell. Biol., 3.","DOI":"10.1002\/jex2.145"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.tibtech.2024.08.007","article-title":"Engineering therapeutical extracellular vesicles for clinical translation","volume":"43","author":"Ma","year":"2025","journal-title":"Trends Biotechnol."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Nakase, I., and Futaki, S. (2015). Combined treatment with a pH-sensitive fusogenic peptide and cationic lipids achieves enhanced cytosolic delivery of exosomes. Sci. Rep., 5.","DOI":"10.1038\/srep10112"},{"key":"ref_102","first-page":"27","article-title":"Extracellular vesicles as tools and targets in therapy for diseases. Signal Transduct","volume":"9","author":"Kumar","year":"2024","journal-title":"Target. Ther."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.jhep.2019.09.014","article-title":"Hepatocyte-derived extracellular vesicles promote endothelial inflammation and atherogenesis via microRNA-1","volume":"72","author":"Jiang","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Patel, S., Guo, M.K., Abdul Samad, M., and Howe, K.L. (2023). Extracellular vesicles as biomarkers and modulators of atherosclerosis pathogenesis. Front. Cardiovasc. Med., 10.","DOI":"10.3389\/fcvm.2023.1202187"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"112808","DOI":"10.1016\/j.celrep.2023.112808","article-title":"Efferocytes release extracellular vesicles to resolve inflammation and tissue injury via prosaposin-GPR37 signaling","volume":"42","author":"Bhattacharya","year":"2023","journal-title":"Cell Rep."},{"key":"ref_106","first-page":"991","article-title":"Calcific aortic valve disease augments vesicular microRNA-145-5p to regulate the calcification of valvular interstitial cells via cellular crosstalk. Basic Res","volume":"120","author":"Goody","year":"2025","journal-title":"Cardiol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"202206187","DOI":"10.1002\/advs.202206187","article-title":"Lipid Nanoparticles Deliver the Therapeutic VEGFA mRNA In Vitro and In Vivo and Transform Extracellular Vesicles for Their Functional Extensions","volume":"10","author":"Nawaz","year":"2023","journal-title":"Adv. Sci."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"e12057","DOI":"10.1002\/jev2.12057","article-title":"Covalent conjugation of extracellular vesicles with peptides and nanobodies for targeted therapeutic delivery","volume":"10","author":"Pham","year":"2021","journal-title":"J. Extracell. Vesicles"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Park, D.J., Duggan, E., Ho, K., Dorschner, R.A., Dobke, M., Nolan, J.P., and Eliceiri, B.P. (2022). Serpin-loaded extracellular vesicles promote tissue repair in a mouse model of impaired wound healing. J. Nanobiotechnol., 20.","DOI":"10.1186\/s12951-022-01656-7"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/s41565-023-01522-z","article-title":"Entry and exit of extracellular vesicles to and from the blood circulation","volume":"19","author":"Iannotta","year":"2024","journal-title":"Nat. Nanotechnol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"170","DOI":"10.20517\/evcna.2023.12","article-title":"Biodistribution of therapeutic extracellular vesicles","volume":"4","author":"Gupta","year":"2023","journal-title":"Extracell. Vesicles Circ. Nucl. Acids"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"e70005","DOI":"10.1002\/jev2.70005","article-title":"Extracellular vesicles, RNA sequencing, and bioinformatic analyses: Challenges, solutions, and recommendations","volume":"13","author":"Miceli","year":"2024","journal-title":"J. Extracell. Vesicles"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1016\/j.ymthe.2023.01.021","article-title":"Extracellular vesicles: The next generation in gene therapy delivery","volume":"31","author":"Cecchin","year":"2023","journal-title":"Mol. Ther."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1177\/0022034518764411","article-title":"Emerging Role of Extracellular Vesicles in Bone Remodeling","volume":"97","author":"Liu","year":"2018","journal-title":"J. Dent. Res."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Blaser, M.C., and Aikawa, E. (2018). Roles and Regulation of Extracellular Vesicles in Cardiovascular Mineral Metabolism. Front. Cardiovasc. Med., 5.","DOI":"10.3389\/fcvm.2018.00187"},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Li, Y., Xing, L., Zhu, M., Li, X., Wei, F., Sun, W., and Jia, Y. (2025). HPMA Copolymers: A Versatile Platform for Targeted Peptide Drug Delivery. Biomolecules, 15.","DOI":"10.3390\/biom15040596"},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Wu, R., Fan, X., Wang, Y., Shen, M., Zheng, Y., Zhao, S., and Yang, L. (2022). Mesenchymal Stem Cell-Derived Extracellular Vesicles in Liver Immunity and Therapy. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.833878"},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Tr\u0119bacz, H., and Barzycka, A. (2023). Mechanical Properties and Functions of Elastin: An Overview. Biomolecules, 13.","DOI":"10.3390\/biom13030574"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Yu, W., Zhu, X., Liu, J., and Zhou, J. (2023). Biofunctionalized Decellularized Tissue-Engineered Heart Valve with Mesoporous Silica Nanoparticles for Controlled Release of VEGF and RunX2-siRNA against Calcification. Bioengineering, 10.","DOI":"10.3390\/bioengineering10070859"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Voicu, G., Mocanu, C.A., Safciuc, F., Anghelache, M., Deleanu, M., Cecoltan, S., Pinteala, M., Uritu, C.M., Droc, I., and Simionescu, M. (2023). Nanocarriers of shRNA-Runx2 directed to collagen IV as a nanotherapeutic system to target calcific aortic valve disease. Mater. Today Bio, 20.","DOI":"10.1016\/j.mtbio.2023.100620"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"9988","DOI":"10.7150\/thno.64229","article-title":"Exosome-mediated delivery of inflammation-responsive Il-10 mRNA for controlled atherosclerosis treatment","volume":"11","author":"Bu","year":"2021","journal-title":"Theranostics"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1038\/s12276-023-00986-2","article-title":"Mesenchymal stem cell-derived extracellular vesicles protect against abdominal aortic aneurysm formation by inhibiting NET-induced ferroptosis","volume":"55","author":"Chen","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_123","first-page":"17","article-title":"Transcriptome analysis reveals therapeutic potential of NAMPT in protecting against abdominal aortic aneurysm in human and mouse","volume":"34","author":"Ouyang","year":"2024","journal-title":"Bioact. Mater."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Stavrou, A., and Ortiz, A. (2022). Extracellular Vesicles: A Novel Tool in Nanomedicine and Cancer Treatment. Cancers, 14.","DOI":"10.3390\/cancers14184450"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Wang, G., Ma, X., Huang, W., Wang, S., Lou, A., Wang, J., Tu, Y., Cui, W., Zhou, W., and Zhang, W. (2024). Macrophage biomimetic nanoparticle-targeted functional extracellular vesicle micro-RNAs revealed via multiomics analysis alleviate sepsis-induced acute lung injury. J. Nanobiotechnol., 22.","DOI":"10.1186\/s12951-024-02597-z"},{"key":"ref_126","first-page":"984","article-title":"Circulating small extracellular vesicles promote proliferation and migration of vascular smooth muscle cells via AXL and MerTK activation. Acta Pharmacol","volume":"44","author":"Lee","year":"2023","journal-title":"Sin."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1186\/s12934-023-02171-6","article-title":"Extracellular vesicles produced by avian pathogenic Escherichia coli (APEC) activate macrophage proinflammatory response and neutrophil extracellular trap (NET) formation through TLR4 signaling","volume":"22","author":"Wang","year":"2023","journal-title":"Microb. Cell Factories"},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Ortmann, W., Such, A., Cichon, I., Baj-Krzyworzeka, M., Weglarczyk, K., and Kolaczkowska, E. (2024). Large extracellular vesicle (EV) and neutrophil extracellular trap (NET) interaction captured in vivo during systemic inflammation. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-55081-x"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"e12332","DOI":"10.1002\/jev2.12332","article-title":"First-in-human clinical trial of allogeneic, platelet-derived extracellular vesicles as a potential therapeutic for delayed wound healing","volume":"12","author":"Johnson","year":"2023","journal-title":"J. Extracell. Vesicles"},{"key":"ref_130","first-page":"447","article-title":"Engineered M2 macrophage-derived extracellular vesicles with platelet membrane fusion for targeted therapy of atherosclerosis","volume":"35","author":"Xie","year":"2024","journal-title":"Bioact. Mater."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"3916","DOI":"10.7150\/thno.52496","article-title":"Engineering extracellular vesicles with platelet membranes fusion enhanced targeted therapeutic angiogenesis in a mouse model of myocardial ischemia reperfusion","volume":"11","author":"Li","year":"2021","journal-title":"Theranostics"},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez, D.A., and Vader, P. (2022). Extracellular Vesicle-Based Hybrid Systems for Advanced Drug Delivery. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14020267"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.jss.2014.03.027","article-title":"Matrix metalloproteinase levels in chronic thoracic aortic dissection","volume":"189","author":"Zhang","year":"2014","journal-title":"J. Surg. Res."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"12704","DOI":"10.1096\/fj.201901548R","article-title":"Perivascular adipose tissue\u2013derived extracellular vesicle miR-221-3p mediates vascular remodeling","volume":"33","author":"Li","year":"2019","journal-title":"FASEB J."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"113961","DOI":"10.1016\/j.addr.2021.113961","article-title":"Dosing extracellular vesicles","volume":"178","author":"Gupta","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1161\/CIRCRESAHA.117.309417","article-title":"Methodological Guidelines to Study Extracellular Vesicles","volume":"120","author":"Coumans","year":"2017","journal-title":"Circ. Res."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1161\/CIRCRESAHA.119.316159","article-title":"Reactive Oxygen-Forming Nox5 Links Vascular Smooth Muscle Cell Phenotypic Switching and Extracellular Vesicle-Mediated Vascular Calcification","volume":"127","author":"Furmanik","year":"2020","journal-title":"Circ. Res."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"2939","DOI":"10.1016\/j.ymthe.2024.02.025","article-title":"Therapeutic potential of RNA-enriched extracellular vesicles: The next generation in RNA delivery via biogenic nanoparticles","volume":"32","author":"Muskan","year":"2024","journal-title":"Mol. Ther."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1007\/s10456-025-09983-7","article-title":"Diversity of extracellular vesicle sources in atherosclerosis: Role and therapeutic application","volume":"28","author":"Zhang","year":"2025","journal-title":"Angiogenesis"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"e2504761","DOI":"10.1002\/smll.202504761","article-title":"Extracellular Vesicles in Atherosclerosis: From Pathogenesis to Theranostic Applications","volume":"21","author":"Fang","year":"2025","journal-title":"Small"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.toxlet.2021.04.019","article-title":"Uremic endothelial-derived extracellular vesicles: Mechanisms of formation and their role in cell adhesion, cell migration, inflammation, and oxidative stress","volume":"347","author":"Favretto","year":"2021","journal-title":"Toxicol. Lett."},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Jiapaer, Z., Li, C., Yang, X., Sun, L., Chatterjee, E., Zhang, L., Lei, J., and Li, G. (2023). Extracellular Non-Coding RNAs in Cardiovascular Diseases. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15010155"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s12265-024-10575-x","article-title":"Endothelial Cell-Derived Extracellular Vesicles Allow to Differentiate Between Various Endotypes of INOCA: A Multicentre, Prospective, Cohort Study","volume":"18","author":"Szolc","year":"2025","journal-title":"J. Cardiovasc. Transl. Res."},{"key":"ref_144","unstructured":"ClinicalTrials.gov (2025, October 22). Extracellular Vesicles from Cardiovascular Progenitor Cells in the Treatment of Non-Ischemic Dilated Cardiomyopathy. Identifier NCT05774509, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05774509."},{"key":"ref_145","unstructured":"ClinicalTrials.gov (2025, October 22). Salivary and Plasma Extracellular Vesicle-Associated Long Non-Coding RNAs in Acute and Chronic Heart Failure (SEAL-HF). Identifier NCT06169540, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT06169540."},{"key":"ref_146","unstructured":"ClinicalTrials.gov (2025, October 22). Extracellular Vesicles in Obesity and Cardiometabolic Disease (EVOC). Identifier NCT06408961, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT06408961."},{"key":"ref_147","unstructured":"ClinicalTrials.gov (2025, October 22). Early Valve Replacement in Severe Asymptomatic Aortic Stenosis (EASY-AS). Identifier NCT04204915, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04204915."},{"key":"ref_148","unstructured":"ClinicalTrials.gov (2025, October 22). Extracellular Vesicles from Mesenchymal Cells in the Treatment of Acute Respiratory Failure Syndrome. Identifier NCT06002841, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT06002841."},{"key":"ref_149","unstructured":"ClinicalTrials.gov (2025, October 22). Safety and Efficacy of Mesenchymal Stem Cell Therapy in Patients with Cardiovascular Disease. Identifier NCT04897841, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04897841."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/s00109-021-02037-7","article-title":"Vascular pathologies in chronic kidney disease: Pathophysiological mechanisms and novel therapeutic approaches","volume":"99","author":"Zietzer","year":"2021","journal-title":"J. Mol. Med."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1161\/ATVBAHA.116.308615","article-title":"Biomarkers of Calcific Aortic Valve Disease","volume":"37","author":"Small","year":"2017","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"4901","DOI":"10.1021\/acs.jproteome.1c00549","article-title":"Column-based Technology for CD9-HPLC Immunoaffinity Isolation of Serum Extracellular Vesicles","volume":"20","author":"Zhu","year":"2021","journal-title":"J. Proteome Res."},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Xu, F., Luo, S., Lu, P., Cai, C., Li, W., and Li, C. (2024). Composition, functions, and applications of exosomal membrane proteins. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1408415"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/s41419-019-1605-2","article-title":"The role of extracellular vesicles in renal fibrosis","volume":"10","author":"Jing","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1007\/s00216-022-04362-3","article-title":"Advancement and obstacles in microfluidics-based isolation of extracellular vesicles","volume":"415","author":"Havers","year":"2023","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Chen, S., Tang, R., and Liu, B. (2024). Current Understanding of Cardiovascular Calcification in Patients with Chronic Kidney Disease. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms251810225"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"126534","DOI":"10.1016\/j.talanta.2024.126534","article-title":"Exosomal membrane proteins analysis using a silicon nanowire field effect transistor biosensor","volume":"278","author":"Qin","year":"2024","journal-title":"Talanta"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/s41378-022-00387-x","article-title":"Si nanowire Bio-FET for electrical and label-free detection of cancer cell-derived exosomes","volume":"8","author":"Zhao","year":"2022","journal-title":"Microsyst. Nanoeng."},{"key":"ref_159","first-page":"111","article-title":"Silicon Nanowire Biosensor for Ultrasensitive and Label-Free Direct Detection of miRNAs. Methods Mol","volume":"67","author":"Zhang","year":"2011","journal-title":"Biol."},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Lo Faro, M., Leonardi, A., Priolo, F., Fazio, B., and Irrera, A. (2022). Future Prospects of Luminescent Silicon Nanowires Biosensors. Biosensors, 12.","DOI":"10.3390\/bios12111052"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.1039\/c2ib20200j","article-title":"Delivery of siRNA silencing Runx2 using a multifunctional polymer-lipid nanoparticle inhibits osteogenesis in a cell culture model of heterotopic ossification","volume":"4","author":"Mishra","year":"2012","journal-title":"Integr. Biol."},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Voicu, G., Rebleanu, D., Constantinescu, C.A., Fuior, E.V., Ciortan, L., Droc, I., Uritu, C.M., Pinteala, M., Manduteanu, I., and Simionescu, M. (2020). Nano-Polyplexes Mediated Transfection of Runx2-shRNA Mitigates the Osteodifferentiation of Human Valvular Interstitial Cells. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12060507"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/11\/1548\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T11:59:33Z","timestamp":1762257573000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/11\/1548"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,4]]},"references-count":162,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["biom15111548"],"URL":"https:\/\/doi.org\/10.3390\/biom15111548","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,4]]}}}