biostudies-literatureZhao YGuizhou Science and Technology DepartmentGuizhou Provincial Health and Family Planning CommissionNational Natural Science Foundation of China913039https://www.ebi.ac.uk/biostudies/studies/S-EPMC9649646biostudies-literatureUnknown9N6-methylatidine (m6A) is involved in post-transcriptional metabolism and a variety of pathological processes. However, little is known about the role of m6A in vascular proliferative diseases, particularly in vascular smooth muscle cells (VSMCs) phenotype switching-induced neointimal hyperplasia. In the current study, we discovered that methyltransferase like 3 (METTL3) is a critical candidate for catalyzing a global increase in m6A in response to carotid artery injury and various VSMCs phenotype switching. The inhibited neointimal hyperplasia was obtained after <i>in vivo</i> gene transfer to knock-down <i>Mettl3</i>. <i>In vitro</i> overexpression of <i>Mettl3</i> resulted in increased VSMC proliferation, migration, and reduced contractile gene expression with a global elevation of m6A Frontiers in cardiovascular medicineMethyltransferase like 3-mediated N6-methylatidin methylation inhibits vascular smooth muscle cells phenotype switching <i>via</i> promoting phosphatidylinositol 3-kinase mRNA decay.PMC964964681960066Qiankehe Foundation-ZK [2022] General 67182160047gzwjkj2020-1-063gzwjkj2020-1-0678176004281760072Qiu ZLi CLong XShi BZhao RXia ABai ZShen YZhao YXiong WGu NfalseMethyltransferase like 3-mediated N6-methylatidin methylation inhibits vascular smooth muscle cells phenotype switching <i>via</i> promoting phosphatidylinositol 3-kinase mRNA decay.N6-methylatidine (m6A) is involved in post-transcriptional metabolism and a variety of pathological processes. However, little is known about the role of m6A in vascular proliferative diseases, particularly in vascular smooth muscle cells (VSMCs) phenotype switching-induced neointimal hyperplasia. In the current study, we discovered that methyltransferase like 3 (METTL3) is a critical candidate for catalyzing a global increase in m6A in response to carotid artery injury and various VSMCs phenotype switching. The inhibited neointimal hyperplasia was obtained after <i>in vivo</i> gene transfer to knock-down <i>Mettl3</i>. <i>In vitro</i> overexpression of <i>Mettl3</i> resulted in increased VSMC proliferation, migration, and reduced contractile gene expression with a global elevation of m6A 2022-01-01T00:00:00Z20222026-07-14T14:23:17.853Z2024-11-05T21:58:39.38ZS-EPMC96496463638635810.3389/fcvm.2022.913039