miR-758 mediates oxLDL-dependent vascular endothelial cell damage by suppressing the succinate receptor SUCNR1.

Atherosclerosis is a vascular disease associated with ageing, and its occurrence and development are closely related to the vascular inflammatory response. Oxidized low-density lipoprotein (oxLDL) has distinct effects in atherosclerosis. We aimed to determine the mechanisms underlying these effects. microRNAs including miR-758 were differentially expressed in oxLDL-treated HUVECs or HAECs. Luciferase reporter assay results indicated that SUCNR1 is an important target of miR-758. Expression of SUCNR1 and its downstream components was decreased significantly in ApoE-/- mice. Overexpression of miR-758 could suppress HUVEC proliferation by cell cycle arrest at the G0/G1 phase. miR-758 was overexpressed on HUVECs with markedly reduced capillary tubule formation capacity. Overexpression of miR-758 on HUVECs or HAECs could significantly reduce SUCNR1 (GPR91), SATA3, phosphorylated STAT3 (p-STAT3), and EVGF levels. Thus, oxLDL likely damages vascular endothelial cells by modulating the DLK1-DIO3 genomic imprinted microRNA cluster component miR-758, thereby suppressing expression of SUCNR1/GPR91 and its downstream components.