{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T04:13:11Z","timestamp":1793506391147,"version":"4.5.0"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2008,6,20]]},"abstract":"<jats:p>\n            Vascular smooth muscle cell (VSMC) accumulation is implicated in plaque development. In contrast, VSMC apoptosis is implicated in plaque rupture, coagulation, vessel remodeling, medial atrophy, aneurysm formation, and calcification. Although VSMC apoptosis accompanies multiple pathologies, there is little proof of direct causality, particularly with the low levels of VSMC apoptosis seen in vivo. Using a mouse model of inducible VSMC\u2013specific apoptosis, we demonstrate that low-level VSMC apoptosis during either atherogenesis or within established plaques of apolipoprotein (Apo)E\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice accelerates plaque growth by two-fold, associated with features of plaque vulnerability including a thin fibrous cap and expanded necrotic core. Chronic VSMC apoptosis induced development of calcified plaques in younger animals and promoted calcification within established plaques. In addition, VSMC apoptosis induced medial expansion, associated with increased elastic lamina breaks, and abnormal matrix deposition reminiscent of cystic medial necrosis in humans. VSMC apoptosis prevented outward remodeling associated with atherosclerosis resulting in marked vessel stenosis. We conclude that VSMC apoptosis is sufficient to accelerate atherosclerosis, promote plaque calcification and medial degeneration, prevent expansive remodeling, and promote stenosis in atherosclerosis.\n          <\/jats:p>","DOI":"10.1161\/circresaha.108.175976","type":"journal-article","created":{"date-parts":[[2008,5,23]],"date-time":"2008-05-23T01:40:09Z","timestamp":1211506809000},"page":"1529-1538","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":352,"title":["Chronic Apoptosis of Vascular Smooth Muscle Cells Accelerates Atherosclerosis and Promotes Calcification and Medial Degeneration"],"prefix":"10.1161","volume":"102","author":[{"given":"Murray C.H.","family":"Clarke","sequence":"first","affiliation":[{"name":"From the Division of Cardiovascular Medicine (M.C.H.C., T.D.L., N.F., M.R.B.) and Department of Clinical Pharmacology (J.J.M., A.P.D.), University of Cambridge, Addenbrooke\u2019s Hospital; and Department of Histopathology (M.G.), Papworth Hospital, Cambridge, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trevor D.","family":"Littlewood","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine (M.C.H.C., T.D.L., N.F., M.R.B.) and Department of Clinical Pharmacology (J.J.M., A.P.D.), University of Cambridge, Addenbrooke\u2019s Hospital; and Department of Histopathology (M.G.), Papworth Hospital, Cambridge, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nichola","family":"Figg","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine (M.C.H.C., T.D.L., N.F., M.R.B.) and Department of Clinical Pharmacology (J.J.M., A.P.D.), University of Cambridge, Addenbrooke\u2019s Hospital; and Department of Histopathology (M.G.), Papworth Hospital, Cambridge, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet J.","family":"Maguire","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine (M.C.H.C., T.D.L., N.F., M.R.B.) and Department of Clinical Pharmacology (J.J.M., A.P.D.), University of Cambridge, Addenbrooke\u2019s Hospital; and Department of Histopathology (M.G.), Papworth Hospital, Cambridge, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony P.","family":"Davenport","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine (M.C.H.C., T.D.L., N.F., M.R.B.) and Department of Clinical Pharmacology (J.J.M., A.P.D.), University of Cambridge, Addenbrooke\u2019s Hospital; and Department of Histopathology (M.G.), Papworth Hospital, Cambridge, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Goddard","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine (M.C.H.C., T.D.L., N.F., M.R.B.) and Department of Clinical Pharmacology (J.J.M., A.P.D.), University of Cambridge, Addenbrooke\u2019s Hospital; and Department of Histopathology (M.G.), Papworth Hospital, Cambridge, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin R.","family":"Bennett","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine (M.C.H.C., T.D.L., N.F., M.R.B.) and Department of Clinical Pharmacology (J.J.M., A.P.D.), University of Cambridge, Addenbrooke\u2019s Hospital; and Department of Histopathology (M.G.), Papworth Hospital, Cambridge, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198602203140806"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/362801a0"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0298-222"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)90472-9"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198705283162204"},{"key":"e_1_3_3_6_2","first-page":"993","volume":"150","year":"1997","unstructured":"LopezCandales A, Holmes DR, Liao SX, Scott MJ, Wickline SA, Thompson RW. 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