Resveratrol protects against ox-LDL-induced endothelial dysfunction in atherosclerosis via depending on circ_0091822/miR-106b-5p-mediated upregulation of TLR4

Abstract

Background Atherosclerosis (AS) is the most common inducer of cardiovascular diseases, and resveratrol (RSV) has played a protective function in the endothelial injury of AS. This study was to explore the molecular mechanism of RSV in oxidized low-density lipoprotein (ox-LDL)-mediated endothelial dysfunction. Methods Circ_0091822, microRNA-106b-5p (miR-106b-5p) or toll-like receptor (TLR4) levels were examined using reverse transcription-quantitative polymerase chain reaction assay. Cell viability was detected via Cell Counting Kit-8 assay and angiogenesis was assessed by tube formation assay. Cell apoptosis was determined through flow cytometry. The protein analysis was conducted via western blot. Inflammatory cytokines were measured by enzyme-linked immunosorbent assay. The oxidative injury was evaluated using the commercial kits. The binding detection was performed via dual-luciferase reporter assay and RNA pull-down assay. Results Circ_0091822 was downregulated by RSV in ox-LDL-treated endothelial cells. RSV promoted cell viability and angiogenesis while inhibiting apoptosis, inflammation, and oxidative stress after exposure to ox-LDL. The circ_0091822 knockdown relieved the ox-LDL-induced cell damages. RSV suppressed the ox-LDL-caused endothelial dysfunction via inducing the downregulation of circ_0091822. Circ_0091822 could target miR-106b-5p, and the reversal of circ_0091822 for RSV function was achieved by sponging miR-106b-5p. Circ_0091822 absorbed miR-106b-5p to elevate the level of TLR4. RSV impeded ox-LDL-induced damages by regulating miR-106b-5p/TLR4 axis. Conclusion All these findings suggested that RSV acted as an inhibitory factor in ox-LDL-induced endothelial injury via downregulating circ_0091822 to upregulate miR-106b-5p-related TLR4.