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Inducible Prmt1 ablation in adult vascular smooth muscle leads to contractile dysfunction and aortic dissection

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dc.contributor.authorPyun, Jung-Hoon-
dc.contributor.authorAhn, Byeong-Yun-
dc.contributor.authorVuong, Tuan Anh-
dc.contributor.authorKim, Su Woo-
dc.contributor.authorJo, Yunju-
dc.contributor.authorJeon, Jaehyung-
dc.contributor.authorBaek, Seung Ho-
dc.contributor.authorKim, Jaewon-
dc.contributor.authorPark, Sungsu-
dc.contributor.authorBae, Gyu-Un-
dc.contributor.authorChoi, Jun-Hyuk-
dc.contributor.authorKim, Jae-Ryong-
dc.contributor.authorRyu, Dongryeol-
dc.contributor.authorLee, Sang-Jin-
dc.contributor.authorKang, Jong-Sun-
dc.date.accessioned2022-04-19T09:03:14Z-
dc.date.available2022-04-19T09:03:14Z-
dc.date.issued2021-10-
dc.identifier.issn1226-3613-
dc.identifier.issn2092-6413-
dc.identifier.urihttps://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/146352-
dc.description.abstractVascular smooth muscle cells (VSMCs) have remarkable plasticity in response to diverse environmental cues. Although these cells are versatile, chronic stress can trigger VSMC dysfunction, which ultimately leads to vascular diseases such as aortic aneurysm and atherosclerosis. Protein arginine methyltransferase 1 (Prmt1) is a major enzyme catalyzing asymmetric arginine dimethylation of proteins that are sources of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase. Although a potential role of Prmt1 in vascular pathogenesis has been proposed, its role in vascular function has yet to be clarified. Here, we investigated the role and underlying mechanism of Prmt1 in vascular smooth muscle contractility and function. The expression of PRMT1 and contractile-related genes was significantly decreased in the aortas of elderly humans and patients with aortic aneurysms. Mice with VSMC-specific Prmt1 ablation (smKO) exhibited partial lethality, low blood pressure and aortic dilation. The Prmt1-ablated aortas showed aortic dissection with elastic fiber degeneration and cell death. Ex vivo and in vitro analyses indicated that Prmt1 ablation significantly decreased the contractility of the aorta and traction forces of VSMCs. Prmt1 ablation downregulated the expression of contractile genes such as myocardin while upregulating the expression of synthetic genes, thus causing the contractile to synthetic phenotypic switch of VSMCs. In addition, mechanistic studies demonstrated that Prmt1 directly regulates myocardin gene activation by modulating epigenetic histone modifications in the myocardin promoter region. Thus, our study demonstrates that VSMC Prmt1 is essential for vascular homeostasis and that its ablation causes aortic dilation/dissection through impaired myocardin expression. Heart disease: A switch that helps hearts coordinate contraction A protein that stabilizes the contractile function of cardiac muscle may act as an important safeguard against cardiovascular disorders. Several studies have hinted that the enzyme protein arginine methyltransferase 1 (Prmt1) may help preserve healthy cardiovascular function, and researchers led by Sang-Jin Lee at AniMusCure and Jong-Sun Kang of Sungkyukwan University in Suwon, South Korea, have produced evidence strongly supporting this idea. Mice lacking Prmt1 in their heart muscle exhibited clear signs of cardiac dysfunction including degeneration of the contractile fibers that coordinate beating. The researchers subsequently determined that the absence of Prmt1 causes muscle cells to switch to a type associated with damage repair and synthesis, which is ill-suited to routine heart function. Similar switching has been seen in various heart disorders, and treatments that boost Prmt1 activity could confer robust protection against these disorders.-
dc.format.extent11-
dc.language영어-
dc.language.isoENG-
dc.publisherSPRINGERNATURE-
dc.titleInducible Prmt1 ablation in adult vascular smooth muscle leads to contractile dysfunction and aortic dissection-
dc.typeArticle-
dc.publisher.location영국-
dc.identifier.doi10.1038/s12276-021-00684-x-
dc.identifier.scopusid2-s2.0-85116834126-
dc.identifier.wosid000706055100001-
dc.identifier.bibliographicCitationEXPERIMENTAL AND MOLECULAR MEDICINE, v.53, no.10, pp 1569 - 1579-
dc.citation.titleEXPERIMENTAL AND MOLECULAR MEDICINE-
dc.citation.volume53-
dc.citation.number10-
dc.citation.startPage1569-
dc.citation.endPage1579-
dc.type.docTypeArticle-
dc.identifier.kciidART002765535-
dc.description.isOpenAccessN-
dc.description.journalRegisteredClassscie-
dc.description.journalRegisteredClassscopus-
dc.description.journalRegisteredClasskci-
dc.relation.journalResearchAreaBiochemistry & Molecular Biology-
dc.relation.journalResearchAreaResearch & Experimental Medicine-
dc.relation.journalWebOfScienceCategoryBiochemistry & Molecular Biology-
dc.relation.journalWebOfScienceCategoryMedicine, Research & Experimental-
dc.subject.keywordPlusHISTONE H4-
dc.subject.keywordPlusCELL-
dc.subject.keywordPlusDIFFERENTIATION-
dc.subject.keywordPlusMETHYLATION-
dc.subject.keywordPlusMYOCARDIN-
dc.subject.keywordPlusDEFICIENCY-
dc.subject.keywordPlusANEURYSMS-
dc.subject.keywordPlusGENES-
dc.subject.keywordPlusMICE-
dc.identifier.urlhttps://www.nature.com/articles/s12276-021-00684-x-
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