Author:
Zhang Yuanyuan,Wang Shaojun,Guo Sicong,Zhang Xinzhong,Yang Chuan,Su Guangsheng,Wan Jiye
Abstract
Abstract
Background
Cardiovascular disease was the most common disease among the elderly with high morbidity and mortality. Circ_0004104 was demonstrated to be involved in the regulation of atherosclerosis.
Methods
Quantitative real-time polymerase chain reaction was employed to measure the expression of circ_0004104, miR-942-5p and Rho associated coiled-coil containing protein kinase 2 (ROCK2). Cell proliferation was tested by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Cell apoptosis was measured by flow cytometry, and tube formation assay was used to detect the angiogenesis ability of cells. Western blot assay was performed to assess protein levels. Enzyme‑linked immunosorbent assay was used to detect the release of IL-1β and TNF-α. The relationship between miR-942-5p and circ_0004104 or ROCK2 was identified by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay, and RNA pull-down assay.
Results
Oxidized low-density lipoprotein (ox-LDL) inhibited the proliferation of human umbilical vein endothelial cells (HUVECs) and promoted apoptosis in a dose-dependent manner. Circ_0004104 was increased in serum of atherosclerosis patients and ox-LDL-treated HUVECs, and silence of circ_0004104 promoted the proliferation of ox-LDL-exposed HUVECs and inhibited cell apoptosis. MiR-942-5p downregulation reversed si-circ_0004104-mediated influences in HUVECs upon ox-LDL exposure. ROCK2 was the target of miR-942-5p and circ_0004104 regulated the expression of ROCK2 through sponging miR-942-5p. ROCK2 abated the influences of miR-942-5p in ox-LDL-stimulated HUVECs. Circ_0004104 was increased in the exosomes derived from ox-LDL-exposed HUVECs, and the expression of circ_0004104 was promoted in HUVECs after stimulation with ox-LDL-treated HUVECs cells-derived exosomes.
Conclusion
Circ_0004104 downregulation receded ox-LDL-induced injury in HUVECs through miR-942-5p and ROCK2.
Publisher
Springer Science and Business Media LLC
Subject
Cardiology and Cardiovascular Medicine
Reference34 articles.
1. Benjamin EJ, Muntner P, Alonso A, Bittencourt MS, Callaway CW, Carson AP, et al. Heart disease and stroke statistics-2019 update: a report from the American Heart Association. Circulation. 2019;139(10):e56–528.
2. Flora GD, Nayak MK. A brief review of cardiovascular diseases, associated risk factors and current treatment regimes. Curr Pharm Des. 2019;25(38):4063–84.
3. Zhao Q, Lu YH, Wang X, Zhang XJ. Circ_USP36/miR-182-5p/KLF5 axis regulates the ox-LDL-induced injury in human umbilical vein smooth muscle cells. Am J Transl Res. 2020;12(12):7855–69.
4. Zhang S, Song G, Yuan J, Qiao S, Xu S, Si Z, et al. Circular RNA circ_0003204 inhibits proliferation, migration and tube formation of endothelial cell in atherosclerosis via miR-370-3p/TGFβR2/phosph-SMAD3 axis. J Biomed Sci. 2020;27(1):11.
5. Kong P, Yu Y, Wang L, Dou YQ, Zhang XH, Cui Y, et al. circ-Sirt1 controls NF-κB activation via sequence-specific interaction and enhancement of SIRT1 expression by binding to miR-132/212 in vascular smooth muscle cells. Nucleic Acids Res. 2019;47(7):3580–93.
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