Hydrogen promoted mitochondrial autophagy and alleviated CIH-induced vascular endothelial cell senescence by regulating oxidative stress.

Abstract

Chronic intermittent hypoxia (CIH), a hallmark of obstructive sleep apnea (OSA), accelerates vascular endothelial senescence. Using a CIH mouse model and corresponding cell model, this study examined how molecular hydrogen (H₂) affects endothelial aging. H₂ administration improved aortic pathological changes, restored vasodilatory function, reduced expression of oxidative stress and senescence markers, and elevated autophagy-related protein levels. Echocardiography, aortic ring assays, SA-β-gal staining, DHE staining, and transmission electron microscopy were employed for assessment. Mechanistic experiments showed that Nrf2 silencing diminished H₂'s capacity to attenuate endothelial senescence in the CIH cell model, indicating that H₂ activates mitochondrial autophagy and suppresses oxidative stress through an Nrf2-dependent pathway. These findings provide mechanistic evidence for the potential application of H₂ in OSA-related vascular endothelial aging.

Mechanism

H₂ activates the Nrf2 signaling pathway, which promotes mitochondrial autophagy and reduces CIH-induced oxidative stress, thereby decreasing senescence marker expression and alleviating vascular endothelial cell aging.