Anti-atherosclerotic effects of LncRNA NEXN-AS1 by regulation of canonical inflammasome pathway of pyroptosis via NEXN.

Introduction: Pyroptosis is closely related to many chronic diseases including atherosclerosis, but the potential pathomechanisms are still unclear. This study was aimed at exploring how lncRNAs may contribute to pyroptosis and the potential mechanisms.

Material and methods: We performed in vitro assays to investigate the effects of a relatively newly discovered lncRNA, NEXN-AS1, on pyroptosis. Two types of vascular wall cells, i.e. human vascular smooth muscle cells (VSMCs) and endothelial cells (ECs), were used as cell models in this study. A previously constructed lentivirus vector was used to overexpress lncRNA NEXN-AS1 and a small interfering RNA (siRNA) mimic against NEXN to knockdown NEXN. The mRNA and protein levels of molecules of pyroptosis in the canonical inflammasome pathway, including nucleotide-binding oligomerisation segment-like receptor family 3 (NLRP3), caspase-1, gasdermin D (GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18) were detected using quantitative real-time PCR and Western blot analysis, respectively.

Results: We found that lentivirus-mediated overexpression of lncRNA NEXN-AS1 increased the expression levels of NEXN and markedly reduced the expression of critical molecules involved in pyroptosis, including NLRP3, caspase-1, GSDMD, IL-1β, and IL-18, in both VSMCs and ECs. Furthermore, NEXN knockdown could reverse the effects of lncRNA NEXN-AS1 overexpression on pyroptosis.

Conclusions: lncRNA NEXN-AS1 could act as a target for maintaining endothelium homeostasis, increasing plaque stability, and delaying the progression of atherosclerosis.