Circ CHMP5 aggravates oxidized low-density lipoprotein-induced damage to human umbilical vein endothelial cells through miR-516b-5p/TGFβR2 axis

BACKGROUND: Atherosclerosis (AS) was one of the main causes of death in the elderly, and lesions in human umbilical vein endothelial cells (HUVECs) could lead to AS. CircRNA-charged multivesicular body protein 5 (circ CHMP5) was reported to participate in the progression of AS. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze the levels of circ CHMP5, miR-516b-5p, and transforming growth factor beta receptor 2 (TGF beta R2) in AS patients or ox-LDL-induced HUVECs. 5-Ethynyl-2'-deoxyuridine and cell counting kit-8 assays were performed to detect cell proliferation. Proteins expression was assessed by western blot assay. Cell apoptosis was examined by flow cytometry. Tube formation assay was utilized to measure the tube formation ability of HUVCEs. The targeting relationships between miR-516b-5p and circ CHMP5 or TGF beta R2 were confirmed by dual-luciferase reporter assay and RNA-pull down assay. RESULTS: Circ CHMP5 was enhanced in the serum of AS patients and ox-LDL-exposure HUVECs. Ox-LDL blocked proliferation and tube formation of HUVECs and induced cell apoptosis, and circ CHMP5 knockdown reversed these effects. In addition, circ CHMP5 regulated the growth of ox-LDL-induced HUVECs through miR-516b-5p and TGF beta R2. Moreover, the effects of circ CHMP5 knockdown on ox-LDL-induced HUVECs were obviously recovered by downregulation of miR-516b-5p, and overexpression of TGF beta R2 restored the effects of miR-516b-5p upregulation on ox-LDL-stimulated HUVECs. CONCLUSION: Silence of circ CHMP5 overturned ox-LDL-treated inhibition of HUVECs proliferation and angiogenesis by miR-516b-5p and TGF beta R2. These results provided new solutions for the treatment of AS.