The Protective Effect of UBE2G2 Knockdown Against Atherosclerosis in Apolipoprotein E-Deficient Mice and Its Association with miR-204-5p.

Abstract

Atherosclerosis (AS) is a chronic and progressive inflammatory disease. Ubiquitin-conjugating enzyme E2G 2 (UBE2G2) has been reported to be differentially expressed in subjects with abnormal coronary endothelial function. We intended to further explore the effect of UBE2G2 in AS using apolipoprotein E-deficient (ApoE-/-) mice. Relative UBE2G2 expression in aortic sinus tissues was examined by Real-time reverse transcriptase-polymerase chain reaction and immunohistochemical staining. Atherosclerotic plaque formation was observed through hematoxylin-eosin staining. The protein levels of adhesion biomarkers and inflammatory cytokines was analyzed by western blotting. The direct interaction between UBE2G2 and miR-204-5p was predicted by bioinformatic analysis, and the correlation was analyzed by Pearson's correlation test, and verified by luciferase reporter assay. Human vascular smooth muscle cells (VSMCs) development was detected by 5-ethynyl-2'-deoxyuridine labeling assay and wound healing assays. UBE2G2 was highly expressed in the aortic sinus tissues of high-fat diet-fed ApoE-/- mice. The atherosclerotic plaque formation was increased in ApoE-/- mice, while UBE2G2 knockdown reduced it. Silencing of UBE2G2 also inhibited the expression and protein levels of adhesion biomarkers and inflammatory cytokines in ApoE-/- mice. MiR-204-5p was the upstream effector of UBE2G2 and miR-204-5p overexpression was found to inhibit the proliferation and migration of human VSMCs through regulating UBE2G2 expression. UBE2G2 inhibition attenuated AS in ApoE-/- mice and UBE2G2 expression was negatively regulated by miR-204-5p in human VSMCs.