{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T01:14:41Z","timestamp":1793927681948,"version":"4.8.0"},"reference-count":65,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T00:00:00Z","timestamp":1754956800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology","award":["NSTC 113-2635-B-A49-001"],"award-info":[{"award-number":["NSTC 113-2635-B-A49-001"]}]},{"name":"Ministry of Science and Technology","award":["NSTC 113-2320-B-038-066"],"award-info":[{"award-number":["NSTC 113-2320-B-038-066"]}]},{"name":"Ministry of Science and Technology","award":["NTSC 114-2314-B-A49-025"],"award-info":[{"award-number":["NTSC 114-2314-B-A49-025"]}]},{"name":"Ministry of Science and Technology","award":["114TMUH-C01-4"],"award-info":[{"award-number":["114TMUH-C01-4"]}]},{"name":"Ministry of Science and Technology","award":["TSGH-C03-112036"],"award-info":[{"award-number":["TSGH-C03-112036"]}]},{"name":"Taipei Medical University Hospital","award":["NSTC 113-2635-B-A49-001"],"award-info":[{"award-number":["NSTC 113-2635-B-A49-001"]}]},{"name":"Taipei Medical University Hospital","award":["NSTC 113-2320-B-038-066"],"award-info":[{"award-number":["NSTC 113-2320-B-038-066"]}]},{"name":"Taipei Medical University Hospital","award":["NTSC 114-2314-B-A49-025"],"award-info":[{"award-number":["NTSC 114-2314-B-A49-025"]}]},{"name":"Taipei Medical University Hospital","award":["114TMUH-C01-4"],"award-info":[{"award-number":["114TMUH-C01-4"]}]},{"name":"Taipei Medical University Hospital","award":["TSGH-C03-112036"],"award-info":[{"award-number":["TSGH-C03-112036"]}]},{"name":"Tri-Service General Hospital","award":["NSTC 113-2635-B-A49-001"],"award-info":[{"award-number":["NSTC 113-2635-B-A49-001"]}]},{"name":"Tri-Service General Hospital","award":["NSTC 113-2320-B-038-066"],"award-info":[{"award-number":["NSTC 113-2320-B-038-066"]}]},{"name":"Tri-Service General Hospital","award":["NTSC 114-2314-B-A49-025"],"award-info":[{"award-number":["NTSC 114-2314-B-A49-025"]}]},{"name":"Tri-Service General Hospital","award":["114TMUH-C01-4"],"award-info":[{"award-number":["114TMUH-C01-4"]}]},{"name":"Tri-Service General Hospital","award":["TSGH-C03-112036"],"award-info":[{"award-number":["TSGH-C03-112036"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease characterized by chronic inflammation, extracellular matrix degradation, and smooth muscle cell apoptosis. Porphyromonas gingivalis (P. gingivalis), a key periodontal pathogen, has been implicated in the progression of cardiovascular diseases, including AAA, but the underlying mechanisms remain unclear. In this study, we investigated the role of GroEL, a bacterial heat shock protein 60 homolog derived from P. gingivalis, in AAA development. We employed a CaCl2-induced AAA mouse model to evaluate the in vivo effects of GroEL. Mice received periaortic CaCl2 application followed by intravenous injections of recombinant GroEL. Histological analyses were performed to assess aneurysmal dilation, elastin degradation, and inflammatory cell infiltration. Flow cytometry and immunohistochemistry were used to determine macrophage phenotypes, while cytokine profiles were quantified via ELISA. In vitro, THP-1 monocytes were treated with GroEL to evaluate its impact on macrophage polarization and cytokine expression. Our results showed that GroEL administration significantly enhanced aortic diameter expansion and elastin breakdown, accompanied by increased infiltration of M1-like macrophages and elevated levels of pro-inflammatory cytokines such as TNF-\u03b1 and IL-6. In vitro findings confirmed that GroEL promotes M1 polarization and inhibits M2 marker expression in THP-1-derived macrophages. These findings suggest that P. gingivalis-derived GroEL plays a pathogenic role in AAA by modulating macrophage polarization toward a pro-inflammatory phenotype. Targeting microbial components such as GroEL may offer new therapeutic strategies for AAA management.<\/jats:p>","DOI":"10.3390\/ijms26167781","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T07:45:31Z","timestamp":1755071131000},"page":"7781","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Porphyromonas gingivalis GroEL Accelerates Abdominal Aortic Aneurysm Formation by Induction of M1 Polarization in Macrophages"],"prefix":"10.3390","volume":"26","author":[{"given":"Yi-Wen","family":"Lin","sequence":"first","affiliation":[{"name":"Institute of Oral Biology, National Yang Ming Chiao Tung University (Taipei Campus), Taipei 112, Taiwan"},{"name":"Taipei Heart Institute, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Ting","family":"Tsai","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Surgery, Tri-Service General Hospital, National Defense Medical University, Taipei 115, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Jen","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Life Science, Fu Jen Catholic University, New Taipei City 242, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Ming","family":"Shih","sequence":"additional","affiliation":[{"name":"Taipei Heart Institute, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Division of Cardiology and Cardiovascular Research Center, Taipei Medical University Hospital, Taipei 110, Taiwan"},{"name":"Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Yao","family":"Huang","sequence":"additional","affiliation":[{"name":"Taipei Heart Institute, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Division of Cardiology and Cardiovascular Research Center, Taipei Medical University Hospital, Taipei 110, Taiwan"},{"name":"Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Department of Biomedical Sciences and Engineering, National Central University, Taoyuan 320, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Sung","family":"Tsai","sequence":"additional","affiliation":[{"name":"Taipei Heart Institute, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Division of Cardiovascular Surgery, Tri-Service General Hospital, National Defense Medical University, Taipei 115, Taiwan"},{"name":"Department and Graduate Institute of Pharmacology, National Defense Medical University, Taipei 115, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Ying","family":"Sung","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Surgery, Tri-Service General Hospital, National Defense Medical University, Taipei 115, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ze-Hao","family":"Lai","sequence":"additional","affiliation":[{"name":"Institute of Oral Biology, National Yang Ming Chiao Tung University (Taipei Campus), Taipei 112, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Science, College of Medicine, University of Arizona, Phoenix, AZ 85721, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4939-2899","authenticated-orcid":false,"given":"Feng-Yen","family":"Lin","sequence":"additional","affiliation":[{"name":"Taipei Heart Institute, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Division of Cardiology and Cardiovascular Research Center, Taipei Medical University Hospital, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ding, F., Wu, D., Han, X., Cheng, L.J., Sun, Z., and Lv, Y.L. (2018). Oral hygiene and periodontal conditions in the Chinese patients with aortic aneurysm. BMC Oral Health, 18.","DOI":"10.1186\/s12903-018-0594-3"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1536\/ihj.13-301","article-title":"High incidence of periodontitis in Japanese patients with abdominal aortic aneurysm","volume":"55","author":"Suzuki","year":"2014","journal-title":"Int. Heart J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1007\/s00380-014-0507-6","article-title":"Incidence of periodontitis in Japanese patients with cardiovascular diseases: A comparison between abdominal aortic aneurysm and arrhythmia","volume":"30","author":"Suzuki","year":"2015","journal-title":"Heart Vessel."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s00011-025-02027-2","article-title":"RAGE deficiency ameliorates abdominal aortic aneurysm progression","volume":"74","author":"Bi","year":"2025","journal-title":"Inflamm. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.ejvs.2004.08.010","article-title":"Detection and localization of periodontopathic bacteria in abdominal aortic aneurysms","volume":"28","author":"Kurihara","year":"2004","journal-title":"Eur. J. Vasc. Endovasc. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Kregielczak, A., Dorocka-Bobkowska, B., Slomski, R., Oszkinis, G., and Krasinski, Z. (2022). Periodontal status and the incidence of selected bacterial pathogens in periodontal pockets and vascular walls in patients with atherosclerosis and abdominal aortic aneurysms. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0270177"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1902\/jop.2005.76.4.590","article-title":"Detection of Actinobacillus actinomycetemcomitans but not bacteria of the red complex in aortic aneurysms by multiplex polymerase chain reaction","volume":"76","author":"Caugant","year":"2005","journal-title":"J. Periodontol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1128\/JCM.39.3.1114-1117.2001","article-title":"Detection of Treponema denticola in atherosclerotic lesions","volume":"39","author":"Okuda","year":"2001","journal-title":"J. Clin. Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5337","DOI":"10.1128\/IAI.66.11.5337-5343.1998","article-title":"Invasion of aortic and heart endothelial cells by Porphyromonas gingivalis","volume":"66","author":"Deshpande","year":"1998","journal-title":"Infect. Immun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1159\/000024499","article-title":"Invasion strategies of the oral pathogen Porphyromonas gingivalis: Implications for cardiovascular disease","volume":"18","author":"Deshpande","year":"1998","journal-title":"Invasion Metastasis"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/j.1348-0421.2000.tb01241.x","article-title":"Porphyromonas gingivalis fimbriae induce adhesion of monocytic cell line U937 to endothelial cells","volume":"44","author":"Hirose","year":"2000","journal-title":"Microbiol. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1128\/IAI.70.1.257-267.2002","article-title":"Fimbria-dependent activation of cell adhesion molecule expression in Porphyromonas gingivalis-infected endothelial cells","volume":"70","author":"Khlgatian","year":"2002","journal-title":"Infect. Immun."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Delbosc, S., Alsac, J.M., Journe, C., Louedec, L., Castier, Y., Bonnaure-Mallet, M., Ruimy, R., Rossignol, P., Bouchard, P., and Michel, J.B. (2011). Porphyromonas gingivalis participates in pathogenesis of human abdominal aortic aneurysm by neutrophil activation. Proof of concept in rats. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0018679"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.atherosclerosis.2011.05.002","article-title":"Protease activity in the multi-layered intra-luminal thrombus of abdominal aortic aneurysms","volume":"218","author":"Folkesson","year":"2011","journal-title":"Atherosclerosis"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1196\/annals.1383.044","article-title":"The intraluminal thrombus as a source of proteolytic activity","volume":"1085","author":"Swedenborg","year":"2006","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"H1168","DOI":"10.1152\/ajpheart.00296.2017","article-title":"Role of myeloperoxidase in abdominal aortic aneurysm formation: Mitigation by taurine","volume":"313","author":"Kim","year":"2017","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3011","DOI":"10.1161\/ATVBAHA.111.237537","article-title":"Proteomic analysis of polymorphonuclear neutrophils identifies catalase as a novel biomarker of abdominal aortic aneurysm: Potential implication of oxidative stress in abdominal aortic aneurysm progression","volume":"31","author":"Lopez","year":"2011","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1161\/01.ATV.0000257552.94483.14","article-title":"Role of oxidative stress in the pathogenesis of abdominal aortic aneurysms","volume":"27","author":"McCormick","year":"2007","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1111\/omi.12083","article-title":"The GroEL protein of Porphyromonas gingivalis accelerates tumor growth by enhancing endothelial progenitor cell function and neovascularization","volume":"30","author":"Lin","year":"2015","journal-title":"Mol. Oral Microbiol."},{"key":"ref_20","first-page":"384","article-title":"The GroEL protein of Porphyromonas gingivalis regulates atherogenic phenomena in endothelial cells mediated by upregulating toll-like receptor 4 expression","volume":"8","author":"Huang","year":"2016","journal-title":"Am. J. Transl. Res."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Lin, F.Y., Hsiao, F.P., Huang, C.Y., Shih, C.M., Tsao, N.W., Tsai, C.S., Yang, S.F., Chang, N.C., Hung, S.L., and Lin, Y.W. (2014). Porphyromonas gingivalis GroEL induces osteoclastogenesis of periodontal ligament cells and enhances alveolar bone resorption in rats. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0102450"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1046\/j.1365-2168.1998.00714.x","article-title":"Epidemiology and potential for prevention of abdominal aortic aneurysm","volume":"85","author":"Wilmink","year":"1998","journal-title":"Br. J. Surg."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Lu, H.Y., Huang, C.Y., Shih, C.M., Chang, W.H., Tsai, C.S., Lin, F.Y., and Shih, C.C. (2015). Dipeptidyl peptidase-4 inhibitor decreases abdominal aortic aneurysm formation through GLP-1-dependent monocytic activity in mice. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0121077"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1016\/j.jvs.2016.05.093","article-title":"A potential contribution of dipeptidyl peptidase-4 by the mediation of monocyte differentiation in the development and progression of abdominal aortic aneurysms","volume":"66","author":"Lu","year":"2017","journal-title":"J. Vasc. Surg."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Salhi, L., Rijkschroeff, P., Van Hede, D., Laine, M.L., Teughels, W., Sakalihasan, N., and Lambert, F. (2021). Blood Biomarkers and Serologic Immunological Profiles Related to Periodontitis in Abdominal Aortic Aneurysm Patients. Front. Cell. Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.766462"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Lin, Y.W., Lin, F.Y., Lai, Z.H., Tsai, C.S., Tsai, Y.T., Huang, Y.S., and Liu, C.W. (Mol. Oral Microbiol., 2024). Porphyromonas gingivalis GroEL accelerates abdominal aortic aneurysm formation by matrix metalloproteinase-2 SUMOylation in vascular smooth muscle cells: A novel finding for the activation of MMP-2, Mol. Oral Microbiol., Online ahead of print.","DOI":"10.1111\/omi.12487"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1186\/s12967-018-1731-0","article-title":"Diverse roles of macrophage polarization in aortic aneurysm: Destruction and repair","volume":"16","author":"Cheng","year":"2018","journal-title":"J. Transl. Med."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Sun, X., Gao, J., Meng, X., Lu, X., Zhang, L., and Chen, R. (2021). Polarized Macrophages in Periodontitis: Characteristics, Function, and Molecular Signaling. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.763334"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Bianchi, S., Torge, D., Rinaldi, F., Piattelli, M., Bernardi, S., and Varvara, G. (2022). Platelets\u2019 Role in Dentistry: From Oral Pathology to Regenerative Potential. Biomedicines, 10.","DOI":"10.3390\/biomedicines10020218"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s12276-019-0286-3","article-title":"Extracellular matrix, regional heterogeneity of the aorta, and aortic aneurysm","volume":"51","author":"Jana","year":"2019","journal-title":"Exp. Mol. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.ejvs.2005.10.030","article-title":"Chronic inflammation, immune response, and infection in abdominal aortic aneurysms","volume":"31","author":"Lindholt","year":"2006","journal-title":"Eur. J. Vasc. Endovasc. Surg."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1253\/circj.CJ-13-0467","article-title":"Effect of toll-like receptor in periodontal bacteria-accelerated abdominal aortic aneurysms","volume":"77","author":"Nakagomi","year":"2013","journal-title":"Circ. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s100169900144","article-title":"Expression of matrix metalloproteinases and TIMPs in human abdominal aortic aneurysms","volume":"12","author":"Elmore","year":"1998","journal-title":"Ann. Vasc. Surg."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1185\/030079904125003143","article-title":"Matrix metalloproteinases: Contribution to pathogenesis, diagnosis, surveillance and treatment of abdominal aortic aneurysms","volume":"20","author":"Kadoglou","year":"2004","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.2353\/ajpath.2009.080845","article-title":"Nitric oxide induces the progression of abdominal aortic aneurysms through the matrix metalloproteinase inducer EMMPRIN","volume":"175","author":"Lizarbe","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Lee, K.Y. (2019). M1 and M2 polarization of macrophages: A mini-review. Med. Biol. Sci. Eng., 2.","DOI":"10.30579\/mbse.2019.2.1.1"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Tsai, C.S., Lin, Y.W., Huang, C.Y., Shih, C.M., Tsai, Y.T., Tsao, N.W., Lin, C.S., Shih, C.C., Jeng, H., and Lin, F.Y. (2016). Thrombomodulin regulates monocye differentiation via PKCdelta and ERK1\/2 pathway in vitro and in atherosclerotic artery. Sci. Rep., 6.","DOI":"10.1038\/srep38421"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1161\/01.ATV.0000214999.12921.4f","article-title":"Inflammation and cellular immune responses in abdominal aortic aneurysms","volume":"26","author":"Shimizu","year":"2006","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1067\/mva.2001.116966","article-title":"Pathogenesis of abdominal aortic aneurysms: A multidisciplinary research program supported by the National Heart, Lung, and Blood Institute","volume":"34","author":"Wassef","year":"2001","journal-title":"J. Vasc. Surg."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1053\/ejvs.2000.1211","article-title":"Activity of matrix metalloproteinase-2 and -9 in abdominal aortic aneurysms. Relation to size and rupture","volume":"20","author":"Petersen","year":"2000","journal-title":"Eur. J. Vasc. Endovasc. Surg."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1067\/mva.2000.109743","article-title":"Increased amount of type III pN-collagen in human abdominal aortic aneurysms: Evidence for impaired type III collagen fibrillogenesis","volume":"32","author":"Bode","year":"2000","journal-title":"J. Vasc. Surg."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1161\/01.ATV.0000064372.78561.A5","article-title":"Elastogenesis in human arterial disease: A role for macrophages in disordered elastin synthesis","volume":"23","author":"Krettek","year":"2003","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.ejvs.2008.11.027","article-title":"Expansion of small-diameter abdominal aortic aneurysms is not reflected by the release of inflammatory mediators IL-6, MMP-9 and CRP in plasma","volume":"37","author":"Karlsson","year":"2009","journal-title":"Eur. J. Vasc. Endovasc. Surg."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e000065","DOI":"10.1161\/JAHA.112.000065","article-title":"CD14 directs adventitial macrophage precursor recruitment: Role in early abdominal aortic aneurysm formation","volume":"2","author":"Blomkalns","year":"2013","journal-title":"J. Am. Heart Assoc."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1161\/CIRCULATIONAHA.113.006320","article-title":"Neurofibromin-deficient myeloid cells are critical mediators of aneurysm formation in vivo","volume":"129","author":"Li","year":"2014","journal-title":"Circulation"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1161\/ATVBAHA.112.247866","article-title":"Macrophage-derived angiopoietin-like protein 2 accelerates development of abdominal aortic aneurysm","volume":"32","author":"Tazume","year":"2012","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1161\/ATVBAHA.114.303353","article-title":"Recent highlights of ATVB: Aneurysms","volume":"34","author":"Daugherty","year":"2014","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"15312","DOI":"10.1016\/S0021-9258(18)82471-1","article-title":"Sequences required for thrombomodulin cofactor activity within the fourth epidermal growth factor-like domain of human thrombomodulin","volume":"268","author":"Lentz","year":"1993","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2511","DOI":"10.1161\/01.ATV.20.12.2511","article-title":"Thrombin activatable fibrinolysis inhibitor and an antifibrinolytic pathway","volume":"20","author":"Bajzar","year":"2000","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s004030050171","article-title":"Thrombomodulin, a functional surface protein on human keratinocytes, is regulated by retinoic acid","volume":"289","author":"Senet","year":"1997","journal-title":"Arch. Dermatol. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1093\/oxfordjournals.jbchem.a122523","article-title":"Functionally active thrombomodulin is present in human platelets","volume":"104","author":"Suzuki","year":"1988","journal-title":"J. Biochem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3128","DOI":"10.1182\/blood.V78.12.3128.3128","article-title":"Thrombomodulin expression by human blood monocytes and by human synovial tissue lining macrophages","volume":"78","author":"McCachren","year":"1991","journal-title":"Blood"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1182\/blood.V77.3.515.515","article-title":"Expression of thrombomodulin by smooth muscle cells in culture: Different effects of tumor necrosis factor and cyclic adenosine monophosphate on thrombomodulin expression by endothelial cells and smooth muscle cells in culture","volume":"77","author":"Soff","year":"1991","journal-title":"Blood"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1016\/j.cardfail.2010.06.415","article-title":"Thrombomodulin is upregulated in cardiomyocytes during cardiac hypertrophy and prevents the progression of contractile dysfunction","volume":"16","author":"Li","year":"2010","journal-title":"J. Card. Fail."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2889","DOI":"10.1182\/blood-2011-03-341222","article-title":"Thrombomodulin is a determinant of metastasis through a mechanism linked to the thrombin binding domain but not the lectin-like domain","volume":"118","author":"Horowitz","year":"2011","journal-title":"Blood"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1172\/JCI925","article-title":"Thrombomodulin modulates growth of tumor cells independent of its anticoagulant activity","volume":"101","author":"Zhang","year":"1998","journal-title":"J. Clin. Investig."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1161\/01.CIR.0000160364.05405.B5","article-title":"Evidence of human thrombomodulin domain as a novel angiogenic factor","volume":"111","author":"Shi","year":"2005","journal-title":"Circulation"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"46750","DOI":"10.1074\/jbc.M305216200","article-title":"Thrombomodulin-mediated cell adhesion: Involvement of its lectin-like domain","volume":"278","author":"Huang","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1161\/01.ATV.0000134298.25489.92","article-title":"Thrombomodulin-protein C-EPCR system: Integrated to regulate coagulation and inflammation","volume":"24","author":"Collen","year":"2004","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1016\/j.biocel.2007.06.024","article-title":"Thrombomodulin: From haemostasis to inflammation and tumourigenesis","volume":"40","author":"Koutsi","year":"2008","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1097\/SHK.0b013e3181d494c4","article-title":"Expression of thrombomodulin on monocytes is associated with early outcomes in patients with coronary artery bypass graft surgery","volume":"34","author":"Tsai","year":"2010","journal-title":"Shock"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1177\/1721727X1401200104","article-title":"The C-Terminal Domain of Thrombomodulin Regulates Monocyte Migration with Interleukin-6 Stimulation","volume":"12","author":"Lin","year":"2014","journal-title":"Eur. J. Inflamm."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.atherosclerosis.2012.09.010","article-title":"The calcium chloride-induced rodent model of abdominal aortic aneurysm","volume":"226","author":"Wang","year":"2013","journal-title":"Atherosclerosis"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1007\/s10557-020-07013-w","article-title":"Dipeptidyl Peptidase-4 Inhibitor Decreases Allograft Vasculopathy Via Regulating the Functions of Endothelial Progenitor Cells in Normoglycemic Rats","volume":"35","author":"Lin","year":"2021","journal-title":"Cardiovasc. Drugs Ther."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.ejvs.2016.07.004","article-title":"Animal models used to explore abdominal aortic aneurysms: A systematic review","volume":"52","author":"Poulsen","year":"2016","journal-title":"Eur. J. Vasc. Endovasc. Surg."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/16\/7781\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:25:34Z","timestamp":1760034334000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/16\/7781"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,12]]},"references-count":65,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["ijms26167781"],"URL":"https:\/\/doi.org\/10.3390\/ijms26167781","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,12]]}}}