{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T21:18:16Z","timestamp":1793049496066,"version":"4.5.0"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2014,9,12]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>Atherosclerosis is a widespread and devastating disease, but the origins of cells within atherosclerotic plaques are not well defined.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>To investigate the specific contribution of vascular smooth muscle cells (SMCs) to atherosclerotic plaque formation by genetic inducible fate mapping in mice.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Methods and Results:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              Vascular SMCs were genetically pulse-labeled using the tamoxifen-dependent Cre recombinase, CreER\n              <jats:sup>T2<\/jats:sup>\n              , expressed from the endogenous SM22\u03b1 locus combined with Cre-activatable reporter genes that were integrated into the ROSA26 locus. Mature SMCs in the arterial media were labeled by tamoxifen treatment of young apolipoprotein E\u2013deficient mice before the development of atherosclerosis and then their fate was monitored in older atherosclerotic animals. We found that medial SMCs can undergo clonal expansion and convert to macrophage-like cells that have lost classic SMC marker expression and make up a major component of advanced atherosclerotic lesions.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>This study provides strong in vivo evidence for smooth muscle-to-macrophage transdifferentiation and supports an important role of SMC plasticity in atherogenesis. Targeting this type of SMC phenotypic conversion might be a novel strategy for the treatment of atherosclerosis, as well as other diseases with a smooth muscle component.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.115.304634","type":"journal-article","created":{"date-parts":[[2014,7,29]],"date-time":"2014-07-29T06:52:22Z","timestamp":1406616742000},"page":"662-667","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":543,"title":["Transdifferentiation of Vascular Smooth Muscle Cells to Macrophage-Like Cells During Atherogenesis"],"prefix":"10.1161","volume":"115","author":[{"given":"Susanne","family":"Feil","sequence":"first","affiliation":[{"name":"From the Interfakult\u00e4res Institut f\u00fcr Biochemie (S.F., F.E., K.S.-O., R.F.), Department of Dermatology (B.F., M.S.), and Pharmakologie, Toxikologie und Klinische Pharmazie (R.L.), University of T\u00fcbingen, T\u00fcbingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"Fehrenbacher","sequence":"additional","affiliation":[{"name":"From the Interfakult\u00e4res Institut f\u00fcr Biochemie (S.F., F.E., K.S.-O., R.F.), Department of Dermatology (B.F., M.S.), and Pharmakologie, Toxikologie und Klinische Pharmazie (R.L.), University of T\u00fcbingen, T\u00fcbingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Lukowski","sequence":"additional","affiliation":[{"name":"From the Interfakult\u00e4res Institut f\u00fcr Biochemie (S.F., F.E., K.S.-O., R.F.), Department of Dermatology (B.F., M.S.), and Pharmakologie, Toxikologie und Klinische Pharmazie (R.L.), University of T\u00fcbingen, T\u00fcbingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Essmann","sequence":"additional","affiliation":[{"name":"From the Interfakult\u00e4res Institut f\u00fcr Biochemie (S.F., F.E., K.S.-O., R.F.), Department of Dermatology (B.F., M.S.), and Pharmakologie, Toxikologie und Klinische Pharmazie (R.L.), University of T\u00fcbingen, T\u00fcbingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Schulze-Osthoff","sequence":"additional","affiliation":[{"name":"From the Interfakult\u00e4res Institut f\u00fcr Biochemie (S.F., F.E., K.S.-O., R.F.), Department of Dermatology (B.F., M.S.), and Pharmakologie, Toxikologie und Klinische Pharmazie (R.L.), University of T\u00fcbingen, T\u00fcbingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Schaller","sequence":"additional","affiliation":[{"name":"From the Interfakult\u00e4res Institut f\u00fcr Biochemie (S.F., F.E., K.S.-O., R.F.), Department of Dermatology (B.F., M.S.), and Pharmakologie, Toxikologie und Klinische Pharmazie (R.L.), University of T\u00fcbingen, T\u00fcbingen, 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