miR-33a-5p Suppresses ox-LDL-Stimulated Calcification of Vascular Smooth Muscle Cells by Targeting METTL3.

Oxidized low-density lipoprotein (ox-LDL) accumulation in the vascular wall plays a pivotal role in the development of atherosclerosis and vascular calcification. However, few studies focus on the regulatory roles of microRNAs in ox-LDL stimulated vascular calcification. The aim of the present study was to investigate how miR-33a-5p regulated vascular calcification stimulated by ox-LDL. In the present study, miR-33a-5p was downregulated during vascular smooth muscle cells (VSMCs) calcification and upon ox-LDL treatment. ox-LDL significantly stimulated VSMCs calcification, while miR-33a-5p overexpression by its mimics transfection inhibited alkaline phosphatase (ALP) activity, mineralization and marker genes associated with VSMCs calcification even in the presence of ox-LDL. Methyltransferase like 3 (METTL3) was the target gene of miR-33a-5p. METTL3 was upregulated during VSMCs calcification and upon ox-LDL treatment. When VSMCs were transfected with miR-33a-5p mimics, METTL3 was downregulated. METTL3 downregulation by siRNA method decreased VSMCs calcification even in the presence of ox-LDL. Taken together, these results suggest miR-33a-5p suppresses VSMCs calcification stimulated by ox-LDL via targeting METTL3, highlighting the critical role of miR-33a-5p/METTL3 in vascular calcification.