{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T15:59:08Z","timestamp":1792425548533,"version":"4.5.0"},"reference-count":55,"publisher":"American Society for Clinical Investigation","issue":"3","license":[{"start":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T00:00:00Z","timestamp":1738540800000},"content-version":"vor","delay-in-days":62,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"crossref","award":["HL151524"],"award-info":[{"award-number":["HL151524"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,3]]},"abstract":"<jats:p>\n                    Disruptions of blood pressure (BP) circadian variation are closely associated with an increased risk of cardiovascular disease. Thus, gaining insights into the molecular mechanisms of BP circadian variation is essential for comprehending BP regulation. Human genetic analyses suggest that PR domain\u2013containing protein 16 (PRDM16), a transcription factor highly expressed in vascular smooth muscle cells (VSMCs), is significantly associated with BP-related traits. However, the roles of PRDM16 in BP regulation are largely unknown. Here, we demonstrate that BP in VSMC-specific\n                    <jats:italic>Prdm16<\/jats:italic>\n                    -KO (\n                    <jats:italic>Prdm16<\/jats:italic>\n                    <jats:sup>SMKO<\/jats:sup>\n                    ) mice was significantly lower than that in control mice during the active period, resulting in aberrant BP circadian variation. Mesenteric artery rings from\n                    <jats:italic>Prdm16<\/jats:italic>\n                    <jats:sup>SMKO<\/jats:sup>\n                    mice showed a reduced response to phenylephrine. Mechanistically, we identified adrenergic receptor \u03b1 1d (\n                    <jats:italic>Adra1d<\/jats:italic>\n                    ) as a transcriptional target of PRDM16. Notably, PRDM16 exhibited a remarkable circadian expression pattern and regulated the expression of clock genes, particularly\n                    <jats:italic>Npas2<\/jats:italic>\n                    , which is crucial for BP circadian variation regulation. Consequently, PRDM16 deficiency in VSMCs caused disrupted BP circadian variation through a reduced response to adrenergic signaling and clock gene regulation. Our findings provide insights into the intricate molecular pathways that govern circadian fluctuations in BP.\n                  <\/jats:p>","DOI":"10.1172\/jci183409","type":"journal-article","created":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T12:00:17Z","timestamp":1733227217000},"source":"Crossref","is-referenced-by-count":23,"title":["Vascular smooth muscle cell PRDM16 regulates circadian variation in blood pressure"],"prefix":"10.1172","volume":"135","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3158-2002","authenticated-orcid":true,"given":"Zhenguo","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjuan","family":"Mu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiyan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan, USA."},{"name":"Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Department of Pathophysiology, Hengyang Medical School, University of South China, Hengyang, Hunan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaozhong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2648-8986","authenticated-orcid":true,"given":"Guizhen","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan, USA."},{"name":"Department of Pharmacological and Pharmaceutical Sciences, University of Houston College of Pharmacy, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3334-9159","authenticated-orcid":true,"given":"Yanhong","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5161-4705","authenticated-orcid":true,"given":"Jifeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida","family":"Surakka","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2357-7825","authenticated-orcid":true,"given":"Y. Eugene","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2024,12,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/hr.2012.26"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-023-01273-1"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)60685-1"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2019.07.008"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01021.2020"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvy023"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.124.323515"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0611680104"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2061"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/nature07182"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2007.06.001"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.121.056666"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00647.2019"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108288"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2023.155658"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.05.015"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.122.010351"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.120.318501"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2023.1165379"},{"key":"B20","doi-asserted-by":"crossref","unstructured":"Kunzhe D, et al. Coronary artery disease risk gene PRDM16 is preferentially expressed in vascular smooth muscle cells and a potential novel regulator of smooth muscle homeostasis [preprint]. https:\/\/doi.org\/10.1101\/2023.04.03.535461 Posted on bioRxiv April 4, 2023","DOI":"10.1101\/2023.04.03.535461"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.167041"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01069-0"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.312086"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0248-z"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3660"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/nm1666"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/s44161-022-00162-1"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0215745"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.029972"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/ng.856"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M808989200"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2018.14"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0267938"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.739227"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1172\/JCI76881"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1093\/database\/baw100"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.13678"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2020.00015"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-018-1775-1"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.167643"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0070109"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-021-00520-6"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05067-4"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.02.057"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12030674"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.smrv.2012.01.006"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101769"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.122.19103"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0011290"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0055844"},{"key":"B51"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.12.021"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.122.20654"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2022.106183"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1172\/JCI158309"}],"container-title":["Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jci.org\/articles\/view\/183409\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T22:49:18Z","timestamp":1779230958000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jci.org\/articles\/view\/183409"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,3]]},"references-count":55,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,12,2]]},"published-print":{"date-parts":[[2025,2,3]]}},"alternative-id":["10.1172\/JCI183409"],"URL":"https:\/\/doi.org\/10.1172\/jci183409","relation":{},"ISSN":["1558-8238"],"issn-type":[{"value":"1558-8238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,3]]},"article-number":"e183409"}}