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

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. [ABSTRACT FROM AUTHOR]