{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:02:30Z","timestamp":1788566550632,"version":"build-2803163510"},"reference-count":51,"publisher":"American Society for Clinical Investigation","issue":"11","license":[{"start":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T00:00:00Z","timestamp":1686182400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["HL151524,HL153710,HL159871,HL162294"],"award-info":[{"award-number":["HL151524,HL153710,HL159871,HL162294"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,8]]},"abstract":"<jats:p>\n                    Abdominal aortic aneurysm (AAA) is usually asymptomatic until life-threatening complications occur, predominantly involving aortic rupture. Currently, no drug-based treatments are available, primarily due to limited understanding of AAA pathogenesis. The transcriptional regulator PR domain\u2013containing protein 16 (PRDM16) is highly expressed in the aorta, but its functions in the aorta are largely unknown. By RNA-seq analysis, we found that vascular smooth muscle cell\u2013specific (VSMC-specific)\n                    <jats:italic>Prdm16<\/jats:italic>\n                    -knockout (\n                    <jats:italic>Prdm16<\/jats:italic>\n                    <jats:sup>SMKO<\/jats:sup>\n                    ) mice already showed extensive changes in the expression of genes associated with extracellular matrix (ECM) remodeling and inflammation in the abdominal aorta under normal housing conditions without any pathological stimuli. Human AAA lesions displayed lower PRDM16 expression. Periadventitial elastase application to the suprarenal region of the abdominal aorta aggravated AAA formation in\n                    <jats:italic>Prdm16<\/jats:italic>\n                    <jats:sup>SMKO<\/jats:sup>\n                    mice. During AAA development, VSMCs undergo apoptosis because of both intrinsic and environmental changes, including inflammation and ECM remodeling.\n                    <jats:italic>Prdm16<\/jats:italic>\n                    deficiency promoted inflammation and apoptosis in VSMCs. A disintegrin and metalloproteinase 12 (ADAM12) is a gelatinase that can degrade various ECMs. We found that ADAM12 is a target of transcriptional repression by PRDM16.\n                    <jats:italic>Adam12<\/jats:italic>\n                    knockdown reversed VSMC apoptosis induced by\n                    <jats:italic>Prdm16<\/jats:italic>\n                    deficiency. Our study demonstrated that PRDM16 deficiency in VSMCs promoted ADAM12 expression and aggravates AAA formation, which may provide potential targets for AAA treatment.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.167041","type":"journal-article","created":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T12:03:16Z","timestamp":1681992196000},"source":"Crossref","is-referenced-by-count":21,"title":["PRDM16 deficiency in vascular smooth muscle cells aggravates abdominal aortic aneurysm"],"prefix":"10.1172","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3158-2002","authenticated-orcid":true,"given":"Zhenguo","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangjie","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, Michigan, USA."},{"name":"Key Laboratory of Animal Cellular and Genetics, Engineering of Heilongjiang Province, College of Life Science, Northeast Agricultural University, Harbin, P.R. 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