MA methylation-mediated elevation of SM22α inhibits the proliferation and migration of vascular smooth muscle cells and ameliorates intimal hyperplasia in type 2 diabetes mellitus.

Abnormal proliferation of vascular smooth muscle cells (VSMCs) induced by insulin resistance facilitates intimal hyperplasia of type 2 diabetes mellitus (T2DM) and N6-methyladenosine (mA) methylation modification mediates the VSMC proliferation. This study aimed to reveal the mA methylation modification regulatory mechanism. In this study, mA demethylase FTO was elevated in insulin-treated VSMCs and T2DM mice with intimal injury. Functionally, FTO knockdown elevated mA methylation level and further restrained VSMC proliferation and migration induced by insulin. Mechanistically, FTO knockdown elevated Smooth muscle 22 alpha (SM22α) expression and mA-binding protein IGF2BP2 enhanced SM22α mRNA stability by recognizing and binding to mA methylation modified mRNA. studies confirmed that the elevated mA modification level of SM22α mRNA mitigated intimal hyperplasia in T2DM mice. Conclusively, mA methylation-mediated elevation of SM22α restrained VSMC proliferation and migration and ameliorated intimal hyperplasia in T2DM.