Abstract:In recent years, methylation of RNA has attracted much attention due to its important role in post-transcriptional regulation of genes. Among them, the m6A modification of RNA is the highest methylation modification except for the 5′cap structure in mRNA. m6A related enzymes are divided into three categories:RNA methyltransferases, RNA demethylases and m6A binding proteins, which play roles in catalytic methylation modification, removal of methylation modification and identification of the methylation site of N6-adenosine, respectively. Then they can help participate in the downstream gene translation, mRNA degradation, control the speed of the RNA nuclear export, and so on. Among these enzymes, methyltransferase-like 3 (METTL3), as the core component of RNA methylation transferases, plays a role in regulating the overall m6A modification of cellular RNA. Cardiovascular diseases are a kind of diseases greatly affected by environmental factors, whereas the latter could affect the occurrence and development through epigenetic related mechanism. Therefore, epigenetics has become a hot issue in the study of cardiovascular disease. The purpose of this review is to briefly summarize the research work related to METTL3 in cardiovascular diseases, which is expected to help the subsequent scientific research and clinical workers to understand the mechanism of m6A in cardiovascular disease development.

Abstract:Aim To investigate the effect of overexpression of methyltransferase-like 3 (METTL3) on myocardial fibrosis. Methods METTL3 protein expression was detected in the myocardium of patients with heart failure (HF) and the healthy donors by Western blot assay. A C57BL/6 mouse model of transverse aortic constriction (TAC) surgery-induced myocardial fibrosis was established, and METTL3 protein expression was detected in the myocardium of TAC mice and sham mice. A cell model of angiotensinⅡ(AngⅡ)-induced myocardial fibrosis in mouse cardiac fibroblasts (CF) was established and used to detect METTL3 expression by Western blot assay. Expression of fibrosis-related genes, including collagen type Ⅰα1 (COL1α1), collagen type Ⅲ α1 (COL3α1) and actin α2 (ACTα2), was detected in mouse CF with adenovirus-mediated overexpression of METTL3. Flow cytometry, EdU and Transwell migration assay were used to detect proliferation and migration activity of mouse CF, respectively. Effects of cardiac specific expression of METTL3 on cardiac function and fibrosis were explored in mice subjected to TAC surgery. Results Protein expression of METTL3 was significantly increased in the myocardium of HF patients (P＜0.05). Consistently, significant up-regulation of METTL3 was observed in the myocardium of TAC mice and AngⅡ-treated mouse CF (P＜0.05, respectively). Overexpression of METTL3 could markedly enhance mouse CF proliferation and migration activities, as well as expression of fibrosis-related genes in mouse CF. Compared with mice in the sham group, significant increase of fibrosis-related gene expression, cardiac fibrosis and cardiac function injury were observed in TAC-induced mice with cardiac specific overexpression of METTL3. Conclusion Overexpression of METTL3 promotes cardiac fibrosis in mice.