RETRACTED ARTICLE: circABCA3 knockdown relieves hypoxia-induced human cardiac microvascular endothelial cell dysfunction by targeting the miR-671-5p/PCSK9 axis.

Abstract

Endothelial cell dysfunction is one of the important stages in the development of acute myocardial infarction (AMI). However, whether circABCA3 (hsa_circ_0037516) mediates AMI development by regulating endothelial cell dysfunction remains unclear. The GEO database (GSE169594 and GSE160717) was used to screen the differentially expressed circRNAs. Hypoxia-induced human cardiac microvascular endothelial cells (HCMECs) were used to mimic AMI cell model. The expression of circABCA3, microRNA (miR)-671-5p, and proprotein convertase subtilisin/kexin type 9 (PCSK9) was detected by quantitative real-time PCR. Cell proliferation, migration, angiogenesis, and apoptosis were measured using cell counting kit 8 assay, EdU assay, transwell assay, wound healing assay, tube formation assay, and flow cytometry. RNA interaction was verified using dual-luciferase reporter assay and RIP assay. The protein expression of PCSK9 and apoptosis-related markers was analyzed by western blot. According to the screening of GEO database, circABCA3 was a highly expressed circRNA in blood samples of AMI patients. circABCA3 was overexpressed in AMI patients and hypoxia-induced HCMECs. Silencing of circABCA3 enhanced proliferation, migration, and angiogenesis and inhibited apoptosis in hypoxia-induced HCMECs. circABCA3 sponged miR-671-5p to positively regulate PCSK9 expression. miR-671-5p inhibitor or PCSK9 overexpression overturned the regulation of circABCA3 knockdown on hypoxia-induced HCMEC dysfunction. circABCA3 might be a potential target for alleviating AMI process, in which knockdown relieved hypoxia-induced HCMEC dysfunction by regulating the miR-671-5p/PCSK9 axis.