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

OBJECTIVES Atherosclerosis is one of the most common cardiovascular diseases and the functional roles of circular RNAs have been discovered in atherosclerosis. Herein, the regulation and mechanism of circ_0002194 were explored in oxidized low-density lipoprotein-induced human vascular endothelial cells. METHODS Circ_0002194, miR-637 and phosphofurin acidic cluster sorting protein 2 levels were determined through reverse transcription-quantitative polymerase chain reaction. Cell viability was detected using cell counting kit-8 assay and angiogenetic ability was analyzed via tube formation assay. Flow cytometry was used for measuring cell apoptosis. Western blot was performed to examine protein expression. Oxidative stress was assessed using the commercial kits. RNA immunoprecipitation assay and dual-luciferase reporter assay were conducted for target analysis. RESULTS Treatment of 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 downregulation of circ_0002194 in cell model. Furthermore, miR-637 was identified as a 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 phosphofurin acidic cluster sorting protein 2 by affecting miR-637. Additionally, miR-637 suppressed endothelial cell damages via partly mediating the expression of phosphofurin acidic cluster sorting protein 2. CONCLUSIONS These evidences demonstrated that circ_0002194 facilitated endothelial cell dysfunction in atherosclerosis partly through upregulating phosphofurin acidic cluster sorting protein 2 by targeting miR-637.

Circular RNA as Therapeutic Targets in Atherosclerosis: Are We Running in Circles?

“…Similar effects were seen in human aortic and umbilical artery VSMCs through a mechanism involving inhibition of miR-637, leading to increased expression of cyclin-dependent kinase 6 (CDK6) [ 61 ]. In opposition to these findings, sponging of miR-637 by circ_0002194 correlated with reduced angiogenesis and increased apoptosis rates of ox-LDL-treated vascular ECs [ 122 ].…”

“…Both (1) harmful and (2) protective effects were seen from sponging of miR-106a-5p [82]. Opposing effects on angiogenesis were also demonstrated via sponging of miR-637 by (4) circHIPK3 and [61] (5) circ_0002194 [122], the latter of which suggests equivocal effects on the pathogenesis of atherosclerosis due to the observed impaired angiogenesis but enhanced oxidative stress. 1) and ( 4) harmful effects of cellular proliferation, migration, and apoptosis [61,82], and ( 2) and (3) protective effects of inhibited osteogenic differentiation, mineralization, and calcium deposition, reduced lipid accumulation, and increased rates of autophagy [37,143].…”

“…Both (1) harmful and (2) protective effects were seen from sponging of miR-106a-5p [ 82 ]. Opposing effects on angiogenesis were also demonstrated via sponging of miR-637 by (4) circHIPK3 and [ 61 ] (5) circ_0002194 [ 122 ], the latter of which suggests equivocal effects on the pathogenesis of atherosclerosis due to the observed impaired angiogenesis but enhanced oxidative stress.…”

Integrating Network Pharmacology and Metabolomics to Explore the Potential Mechanism of Pinolenic Acid against Atherosclerosis

“…Endothelial dysfunction is related to the development and progression of AS [26]. Terefore, improving endothelial function may be an efective method for AS treatment [7].…”