CCAT1 atenúa la piroptosis de células endoteliales asociada a hipoxia intermitente a través de la degradación del
Wen Liu1, Xinxin Li1, Qing Zhu1
1Department of Cardiovascular Ultrasound, The First Hospital of China Medical University, No. 155 NanjingBei Street, Heping District, Shenyang, Liaoning Province, 110001, China; Clinical Medical Research Center of Imaging in Liaoning Province, The First Hospital of China Medical University, No. 155 NanjingBei Street, Heping District, Shenyang, Liaoning Province, 110001, China.
Background:
Previous studies have established that vascular endothelial dysfunction is prevalent among obstructive sleep apnea (OSA) patients. Nonetheless, the mechanism by which intermittent hypoxia (IH) contributes to endothelial dysfunction remains unclear.
Methods:
Bioinformatics analysis was conducted to identify the key molecules implicated in IH. The correlation between serum lncRNA CCAT1 and GSDMD levels with endothelial function in OSA patients was evaluated. IH-induced HUVECs were used as an in vitro OSA model. We assessed the expression and interaction of CCAT1 and IRF1, and their effects on endothelial cell pyroptosis and dysfunction to investigate the mechanism of CCAT1/IRF1/GSDMD in IH-induced HUVECs.
Findings:
Bioinformatic analysis revealed the crucial role of pyroptotic pathway after IH. OSA patients exhibited elevated serum GSDMD levels, however, CCAT1 expression was decreased. There was a correlation between OSA severity, endothelial function, GSDMD and CCAT1 levels. CCAT1 was downregulated and IRF1 was upregulated in IH-induced HUVECs. Low CCAT1 and high IRF1 expression were associated with exacerbated GSDMD-mediated pyroptosis and impaired endothelial function. CCAT1 overexpression facilitated IRF1 mRNA degradation of via SMD pathway, mitigating GSDMD-mediated pyroptosis and endothelial dysfunction.
Interpretation:
CCAT1 attenuates IH-induced endothelial cell pyroptosis through STAU1-mediated IRF1 mRNA degradation, suggesting its potential therapeutic value in OSA-related endothelial dysfunction.
