Knockdown of circ_0002194 protects against oxidized low-density lipoprotein-induced cell damage via the regulation of the miR-637/PACS2 axis in human vascular endothelial cells.

Abstract

OBJECTIVESAtherosclerosis is one of the most common cardiovascular diseases. The functional roles of circular (circ) RNAs have been discovered in atherosclerosis. Our goal was to explore the regulation and mechanism of circ_0002194 in oxidized low-density lipoprotein-induced human vascular endothelial cells.METHODSCirc_0002194, microRNA-637 (miR-637) and phosphofurin acidic cluster sorting protein 2 (PACS2) levels were determined through the reverse transcription-quantitative polymerase chain reaction. Cell viability was detected using the Cell Counting Kit-8 assay, and angiogenetic ability was analysed via the tube formation assay. Flow cytometry was used to measure cell apoptosis. Western blot was performed to examine protein expression. Oxidative stress was assessed using commercial kits. The RNA immunoprecipitation assay and dual-luciferase reporter assay were conducted for target analysis.RESULTSTreatment with oxidized low-density lipoprotein induced the upregulation of circ_0002194 in endothelial cells. Cell viability and angiogenesis were promoted while cell apoptosis and oxidative stress were reduced by the downregulation of circ_0002194 in the cell model. Furthermore, miR-637 was identified as an miRNA target of circ_0002194, and the regulatory role of circ_0002194 was associated with the sponge effect on miR-637. Moreover, circ_0002194 could regulate PACS2 by affecting miR-637. Additionally, miR-637 suppressed endothelial cell damage by partly mediating the expression of PACS2.CONCLUSIONSThe results demonstrated that circ_0002194 facilitated endothelial cell dysfunction in atherosclerosis partly through upregulating PACS2 by targeting miR-637.