{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:22:24Z","timestamp":1792794144055,"version":"4.5.0"},"reference-count":219,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2020,8,31]],"date-time":"2020-08-31T00:00:00Z","timestamp":1598832000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Abdominal aortic aneurysm (AAA) refers to the localized dilatation of the infra-renal aorta, in which the diameter exceeds 3.0 cm. Loss of vascular smooth muscle cells, degradation of the extracellular matrix (ECM), vascular inflammation, and oxidative stress are hallmarks of AAA pathogenesis and contribute to the progressive thinning of the media and adventitia of the aortic wall. With increasing AAA diameter, and left untreated, aortic rupture ensues with high mortality. Collective evidence of recent genetic and epigenetic studies has shown that phenotypic modulation of smooth muscle cells (SMCs) towards dedifferentiation and proliferative state, which associate with the ECM remodeling of the vascular wall and accompanied with increased cell senescence and inflammation, is seen in in vitro and in vivo models of the disease. This review critically analyses existing publications on the genetic and epigenetic mechanisms implicated in the complex role of SMCs within the aortic wall in AAA formation and reflects the importance of SMCs plasticity in AAA formation. Although evidence from the wide variety of mouse models is convincing, how this knowledge is applied to human biology needs to be addressed urgently leveraging modern in vitro and in vivo experimental technology.<\/jats:p>","DOI":"10.3390\/ijms21176334","type":"journal-article","created":{"date-parts":[[2020,8,31]],"date-time":"2020-08-31T21:41:23Z","timestamp":1598910083000},"page":"6334","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":135,"title":["Genetic and Epigenetic Mechanisms Underlying Vascular Smooth Muscle Cell Phenotypic Modulation in Abdominal Aortic Aneurysm"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2400-4220","authenticated-orcid":false,"given":"Rijan","family":"Gurung","sequence":"first","affiliation":[{"name":"Cardiovascular Research Institute, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, NUHS Tower Block, Level 9, Singapore 119228, Singapore"},{"name":"Genome Institute of Singapore, A*STAR, 60 Biopolis Street, Genome, Singapore 138672, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew Mark","family":"Choong","sequence":"additional","affiliation":[{"name":"Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, NUHS Tower Block, Level 8, Singapore 119228, Singapore"},{"name":"Department of Cardiac, Thoracic and Vascular Surgery, National University Hospital, National University Health System, 1E Kent Ridge Road, NUHS Tower Block, Level 9, Singapore 119228, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chin Cheng","family":"Woo","sequence":"additional","affiliation":[{"name":"Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, NUHS Tower Block, Level 8, Singapore 119228, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Foo","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, NUHS Tower Block, Level 9, Singapore 119228, Singapore"},{"name":"Genome Institute of Singapore, A*STAR, 60 Biopolis Street, Genome, Singapore 138672, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4106-3908","authenticated-orcid":false,"given":"Vitaly","family":"Sorokin","sequence":"additional","affiliation":[{"name":"Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, NUHS Tower Block, Level 8, Singapore 119228, Singapore"},{"name":"Department of Cardiac, Thoracic and Vascular Surgery, National University Hospital, National University Health System, 1E Kent Ridge Road, NUHS Tower Block, Level 9, Singapore 119228, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.ejvs.2018.09.020","article-title":"Editor\u2019s choice\u2013European society for vascular surgery (ESVS) 2019 clinical practice guidelines on the management of abdominal aorto-iliac artery aneurysms","volume":"57","author":"Wanhainen","year":"2019","journal-title":"Eur. 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