Abstract: BACKGROUND:Atherosclerosis (AS) is defined as a chronic inflammatory disorder underly the pathogenesis of cardiovascular diseases (CVDs). Endothelial pyroptosis is associated with AS-like diseases and other CVDs. OBJECTIVE:This work was designed to expound on the effect of GATA-binding protein 1 (GATA1) on pyroptosis of human coronary artery endothelial cells (HCAECs) in AS. METHODS:HCAECs were treated with oxidized-low density lipoprotein (ox-LDL) to establish HCAEC injury models. Plasmids for overexpressing GATA1 or silencing retinoic acid-related orphan receptor α (RORα) were transfected into HCAECs. Thereafter, the mRNA levels of GATA1 and RORα in HCAECs were detected using real-time quantitative polymerase chain reaction. HCAEC viability was examined using the cell counting kit-8 method. The levels of pyroptosis-related proteins NOD-like receptor protein 3 (NLRP3), cleaved-Caspase-1, N-terminal of gasdermin D (GSDMD-N), and pyroptosis-related inflammatory cytokines interleukin (IL)-1β and IL-18 were determined using Western blot and enzyme-linked immunosorbent assays, respectively. The targeting relationship between GATA1 and RORα was verified using the chromatin-immunoprecipitation assay. Then, the rescue experiment was conducted to explore the effect of RORα on pyroptosis of ox-LDL-treated HCAECs. RESULTS:In ox-LDL-treated HCAECs, GATA1 and RORα expressions were decreased, HCAEC viability was reduced, and the levels of NLRP3, cleaved-Caspase1, GSDMD-N, IL-1β, and IL-18 were elevated. GATA1 overexpression increased HCAEC viability and attenuated pyroptosis. GATA1 bound to the RORα promoter region to stimulate RORα transcription, and RORα suppression facilitated ox-LDL-induced pyroptosis of HCAECs. CONCLUSIONS:GATA1 activated RORα transcription and therefore limited pyroptosis of ox-LDL-treated HCAECs.
