Circ_0003204 knockdown protects endothelial cells against oxidized low-density lipoprotein-induced injuries by targeting the miR-491-5p-ICAM1 pathway

• Published in: Journal of thrombosis and thrombolysis 2022-02, Vol.53 (2), p.302-312
• Main Authors: Zhang, Dongying, Zhang, Gang, Yu, Kun, Zhang, Xiwen, Jiang, Aixia
• Format: Article
• Language: English
• Subjects: 3' Untranslated regions; Angiogenesis; Apoptosis; Arteriosclerosis; Atherosclerosis; Cardiology; Cell adhesion; Cell culture; Cell Proliferation; Cell viability; Cholecystokinin; Circular RNA; Endothelial cells; Enzyme-linked immunosorbent assay; Flow cytometry; Hematology; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; Intercellular adhesion molecule 1; Intercellular Adhesion Molecule-1 - genetics; Intercellular Adhesion Molecule-1 - metabolism; Lipoproteins, LDL - metabolism; Low density lipoprotein; Medicine; Medicine & Public Health; MicroRNAs - genetics; RNA, Circular - genetics; RNA, Circular - metabolism; Signal Transduction; Umbilical vein
• ISSN: 0929-5305; 1573-742X
• DOI: 10.1007/s11239-021-02606-0

Emerging evidence indicates that circular RNA (circRNA) is implicated in the development of atherosclerosis (AS). This study investigated the effect of circ_0003204 on endothelial cell function and explored the functional mechanism of circ_0003204 in AS progression. AS cell models were constructed by treating human umbilical vein endothelial cells (HUVEC) with oxidized low-density lipoprotein (ox-LDL). The expression of circ_0003204 was detected by quantitative real-time PCR (qPCR). The releases of pro-inflammatory factors were determined by ELISA. Cell viability was checked by CCK-8 assay. Cell apoptosis was monitored by flow cytometry assay. The ability of angiogenesis was assessed by tube formation assay. The protein levels of cell development- and apoptosis-related markers were measured by western blot. The binding relationship between miR-491-5p and circ_0003204 or intercellular adhesion molecule 1 (ICAM1) was verified by dual-luciferase reporter assay or RIP assay. The expression of circ_0003204 was strengthened in ox-LDL-treated HUVECs. Circ_0003204 knockdown inhibited ox-LDL-induced inflammation and cell apoptosis, and promoted ox-LDL-depleted cell viability and tube formation ability in HUVECs. MiR-491-5p was a target of circ_0003204, and miR-491-5p directly bound to ICAM1 3′UTR. Accordingly, circ_0003204 positively regulated ICAM1 expression by targeting miR-491-5p. Rescue experiments presented that miR-491-5p inhibition reversed the effects of circ_0003204 knockdown, and ICAM1 overexpression abolished the effects of miR-491-5p restoration. Circ_0003204 knockdown protects HUVECs against ox-LDL-induced injuries by targeting the miR-491-5p-ICAM1 pathway, hinting that circ_0003204 inhibition might prevent AS development.