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RNA N\n                    <jats:sup>6<\/jats:sup>\n                    \u2010methyladenosine (m\n                    <jats:sup>6<\/jats:sup>\n                    A) methylation has been reported to be involved in the development of various cardiovascular diseases, but whether it has a regulatory effect on neointima formation is unknown. Herein, we revealed that methyltransferase\u2010like 3 (METTL3), the major methyltransferase of m\n                    <jats:sup>6<\/jats:sup>\n                    A methylation, was downregulated during vascular smooth muscle cell (VSMC) proliferation and neointima formation. Knockdown of METTL3 facilitated, while overexpression of METTL3 suppressed the proliferation of human aortic smooth muscle cells (HASMCs) by arresting HASMCs at G2\/M checkpoint and the phosphorylation of CDC2 (p\u2010CDC2) was inactivated by METTL3. On the other hand, the migration and synthetic phenotype of HASMCs were enhanced by METTL3 knockdown, but inhibited by METTL3 overexpression. The protein levels of matrix metalloproteinase 2 (MMP2), MMP7 and MMP9 were reduced, while the expression level of tissue inhibitor of metalloproteinase 3 was increased in HASMCs with METTL3 overexpression. Moreover, METTL3 promoted the autophagosome formation by upregulating the expression of ATG5 (autophagy\u2010related 5) and ATG7. Knockdown of either ATG5 or ATG7 largely reversed the regulatory effects of METTL3 overexpression on phenotypic switching of HASMCs, as evidenced by increased proliferation and migration, and predisposed to synthetic phenotype. These results indicate that METTL3 inhibits the phenotypic switching of VSMCs by positively regulating ATG5\u2010mediated and ATG7\u2010mediated autophagosome formation. Thus, enhancing the level of RNA m\n                    <jats:sup>6<\/jats:sup>\n                    A or the formation of autophagosomes is the promising strategy to delay neointima formation.\n                  <\/jats:p>","DOI":"10.1111\/cpr.13386","type":"journal-article","created":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T22:41:40Z","timestamp":1671835300000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Methyltransferase\u2010like 3 suppresses phenotypic switching of vascular smooth muscle cells by activating autophagosome formation"],"prefix":"10.1111","volume":"56","author":[{"given":"Ze\u2010Min","family":"Fang","sequence":"first","affiliation":[{"name":"Division of Cardiothoracic and Vascular Surgery Sino\u2010Swiss Heart\u2010Lung Transplantation Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu\u2010Min","family":"Zhang","sequence":"additional","affiliation":[{"name":"Cardiac Rehabilitation Center Fuwai Hospital CAMS&amp;PUMC Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanshen","family":"Luo","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic and Vascular Surgery Sino\u2010Swiss Heart\u2010Lung Transplantation Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ding\u2010Sheng","family":"Jiang","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic and Vascular Surgery Sino\u2010Swiss Heart\u2010Lung Transplantation Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan Hubei China"},{"name":"Key Laboratory of Organ Transplantation, Ministry of Education; NHC Key Laboratory of Organ Transplantation; Key Laboratory of Organ Transplantation Chinese Academy of Medical Sciences Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Huo","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic and Vascular Surgery Sino\u2010Swiss Heart\u2010Lung Transplantation Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxuan","family":"Zhong","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic and Vascular Surgery Sino\u2010Swiss Heart\u2010Lung Transplantation Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Feng","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic and Vascular Surgery Sino\u2010Swiss Heart\u2010Lung Transplantation Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenlin","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Cardiology Zhongnan Hospital of Wuhan University Wuhan Hubei China"},{"name":"Institute of Myocardial Injury and Repair Wuhan University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic and Vascular Surgery Sino\u2010Swiss Heart\u2010Lung Transplantation Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaoke","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Cardiology Renmin Hospital of Wuhan University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingliang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Cardiology Renmin Hospital of Wuhan University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Cardiology Zhongnan Hospital of Wuhan University Wuhan Hubei China"},{"name":"Institute of Myocardial Injury and Repair Wuhan University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5884-0657","authenticated-orcid":false,"given":"Xin","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Cardiology Renmin Hospital of Wuhan University Wuhan 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