Long Noncoding RNA AC078850.1 Induces NLRP3 Inflammasome-Mediated Pyroptosis in Atherosclerosis by Upregulating ITGB2 Transcription via Transcription Factor HIF-1 alpha

As a chronic progressive inflammatory disease, atherosclerosis constitutes a leading cause of cardiovascular disease, with high mortality and morbidity worldwide. The effect of lncRNA AC078850.1 in atherosclerosis is unknown; this study aims to explore the regulatory mechanism of the lncRNA AC078850.1/HIF-1 alpha complex in atherosclerosis. Initially, we identified the lncRNA AC078850.1 associated with atherosclerosis using multiple bioinformatic methods, finding that the level of lncRNA AC078850.1 in peripheral blood mononuclear cells was positively related to the severity of carotid atherosclerosis. LncRNA AC078850.1 was upregulated, and found to be predominately localized in the nucleus of THP-1 macrophage-derived foam cells. Both the knockdown of lncRNA AC078850.1 and the transcription factor HIF-1 alpha can each markedly suppress ITGB2 gene transcription, ROS production, NLRP3 inflammasome, IL-1 beta/18 release, lipid accumulation, and pyroptotic cell death in ox-LDL-stimulated THP-1-derived macrophages. Additionally, the downregulation of HIF-1 alpha attenuated the positive effects of lncRNA AC078850.1 on pyroptosis and foam cell formation. In addition, the knockdown of lncRNA AC078850.1 suppressed HIF-1 alpha-aggravated macrophages pyroptosis and foam cell formation. Meanwhile, inhibition of ITGB2 gene expression ameliorated HIF-1 alpha-aggravated ROS generation in THP-1-derived macrophages. Taken together, our study demonstrated that lncRNA AC078850.1 was involved in the regulation of ITGB2 gene transcription by binding to the HIF-1ff and lncRNA AC078850.1/HIF-1 alpha complex, promoting both NLRP3 inflammasome-mediated pyroptosis and foam cell formation through the ROS-dependent pathway in cases of atherosclerosis.