Affiliations: [a] Department of Internal Medicine-Cardiovascular, Shanxi Provincial People’s Hospital, Taiyuan City, Shanxi, China
| [b]
Shanxi Provincial Medical Service Evaluation Center, Taiyuan City, Shanxi, China
| [c] Department of Ultrasound, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, China
| [d] Department of Cardiology, Shanxi Provincial People’s Hospital, Taiyuan City, Shanxi, China
Correspondence:
[*]
Corresponding author: Wuxiao Yang, Department of Cardiology, Shanxi Provincial People’s Hospital, No. 29, Shuangta Temple Street, Taiyuan City, 030012, Shanxi, China. Tel.: +86 0351 4960157; E-mail: [email protected].
Note: [1] These authors contributed equally to this paper.
Abstract: 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 (TGFβR2) 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 TGFβR2 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 TGFβR2. Moreover, the effects of circ_CHMP5 knockdown on ox-LDL-induced HUVECs were obviously recovered by downregulation of miR-516b-5p, and overexpression of TGFβR2 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 TGFβR2. These results provided new solutions for the treatment of AS.
Keywords: Circ_CHMP5, miR-516b-5p, TGFβR2, HUVECs, AS
