LncRNA SRA deregulation contributes to the development of atherosclerosis by causing dysfunction of endothelial cells through repressing the expression of adipose triglyceride lipase.

It has been well established that long non-coding RNAs (lncRNAs) are crucial mediators in a diverse range of diseases, including atherosclerosis. The present study aimed to examine the molecular mechanisms underlying the association between steroid receptor RNA activator (SRA) and atherosclerosis. Reverse transcription-quantitative polymerase chain reaction analysis, western blot analysis and luciferase assays were performed to examine interactions among SRA, adipose triglyceride lipase (ATGL) and peroxisome proliferator-activated receptor (PPAR), and the effect of resveratrol (RSV) on the levels of SRA, ATGL and PPAR. ELISA was performed to determine the effects of SRA and RSV on the production of inflammatory-associated cytokines. The results showed that knockdown of the expression of SRA by transfecting HUVECs with short hairpin RNA-SRA inhibited the production of ATGL and PPAR. A plasmid coding SRA RNA, but not the SRAP protein, attenuated the luciferase activity of the ATGL promoter. PPAR had no effect on the luciferase activity driven by the ATGL promoter in the absence of rosiglitazone, whereas the luciferase activity of the ATGL promoter was elevated in the presence of rosiglitazone. This effect was eliminated by SRA. SRA enhanced the production of inflammatory-associated cytokines, including tumor necrosis factor-, interleukin-6, monocyte chemotactic protein-1 and intercellular adhesion molecule-1; however, the promoting effect of SRA was eliminated by RSV. RSV increased the expression of ATGL and PPAR, but not that of SRA. RSV distinctly and concentration-dependently upregulated the luciferase activity of ATGL, compared with that in the cells without RSV treatment, whereas treating with rosiglitazone inhibited the effect of RSV on the luciferase activity of ATGL. The present study examined the roles of SRA in atherosclerosis, and the effects of changes in SRA and ATGL on inflammatory cytokines and HUVEC dysfunction.