Chronic intermittent hypoxia-induced mitochondrial dysfunction mediates endothelial injury via the TXNIP/NLRP3/IL-1? signaling pathway

Oxidative stress and inflammation induced by chronic intermittent hypoxia (CIH) are trigger factors of cardiovascular diseases in patients with obstructive sleep apnea (OSA). This study aimed to investigate the role of CIHinduced mitochondrial dysfunction in vascular endothelial injury both in vivo and in vitro. Human umbilical vein endothelial cells and Sprague Dawley rats were exposed to CIH. CIH promoted the production of intracellular reactive oxygen species, caused mitochondrial dysfunction, and induced cell apoptosis in human umbilical vein endothelial cells. RNA-Seq analysis revealed that the NOD-like receptor signaling pathway was involved in endothelial injury induced by CIH. TXNIP/NLRP3/IL-1? pathway was found to be upregulated by CIH. Knockdown of TNXIP rescued the endothelial cells from CIH-induced apoptosis, indicating that activation of the TXNIP/NLRP3/IL-1? pathway mediated the CIH-induced endothelial apoptosis. Administration of the mitochondria-targeted antioxidant mito-TEMPO improved mitochondrial function and suppressed upregulation of the TXNIP/NLRP3/IL-1? pathway, thereby alleviating CIH-induced endothelial apoptosis. In vivo experiments confirmed the results, where mito-TEMPO was found to ameliorate endothelial injury in rat aortas exposed to CIH. The results imply that CIH-induced mitochondrial dysfunction mediates endothelial injury implication of TXNIP/NLRP3/IL-1? signaling pathway.

Automated summary

Chronic intermittent hypoxia-induced mitochondrial dysfunction mediates endothelial apoptosis through the TXNIP/NLRP3/IL-1β signaling pathway. Mitochondria-targeted antioxidant mito-TEMPO can improve mitochondrial function and alleviate CIH-induced endothelial apoptosis.