LncRNA ENST00000602558.1 regulates ABCG1 expression and cholesterol efflux from vascular smooth muscle cells through a p65-dependent pathway

Abstract Background and aims Long non-coding RNAs (lncRNAs) have proven to be involved in the progression of atherosclerosis and dyslipidemia. In addition, vascular smooth muscle cells (VSMCs) phenotype switching, including VSMCs-derived foam cells formation, plays a key role in the pathogenesis of atherosclerosis. LncRNA ENST00000602558.1, one of the differentially expressed lncRNAs between coronary artery disease (CAD) patients and healthy controls identified by our previous study, was located to TG and HDL susceptibility loci, but its role and underlying mechanism in the pathogenesis of atherosclerosis remain unclear. The present study aims to explore the role and underlying mechanism of ENST00000602558.1 in the regulation of cholesterol efflux from VSMCs. Methods ABCG1 mRNA and protein expression in VSMCs was detected using qRT-PCR and Western blot, respectively. ABCG1-mediated cholesterol efflux to HDL from VSMCs was measured by means of NBD-cholesterol fluorescence intensity. The binding of ENST00000602558.1 to p65 and p65 to ABCG1 promoter region was detected by RNA immunoprecipitation (RIP) assay and chromatin immunoprecipitation (ChIP) assay, respectively. Results Overexpression of ENST00000602558.1 downregulated ABCG1 mRNA and protein expression, while knockdown of ENST00000602558.1 upregulated ABCG1 mRNA and protein expression. Consistently, ENST00000602558.1 overexpression decreased ABCG1-mediated cholesterol efflux to HDL from VSMCs by 30.38% ( p p  = 0.001). In addition to cholesterol efflux, overexpression of ENST00000602558.1 increased lipid accumulation and TC/TG levels, while knockdown of ENST00000602558.1 decreased lipid accumulation and TC/TG levels in VSMCs. Furthermore, we confirmed that ENST00000602558.1 regulated ABCG1 expression and ABCG1-mediated cholesterol efflux from VSMCs through binding to p65. Conclusions In conclusion, ENST00000602558.1 played an important role in mediating cholesterol efflux to HDL from VSMCs by regulating ABCG1 expression through binding to p65.