Hydrogen sulfide preserves the function of senescent endothelium through SIRT2 mediated inflammatory inhibition.

Endothelial aging is an independent risk factor of cardiovascular diseases, and this study aims to explore the mechanism of endothelial aging. We first applied two animal aging models and two cellular aging models to observe the characteristics of senescent endothelium at the morphological, functional, and molecular levels. It was confirmed that the aging of endothelial cells was accompanied by activation of Nod like receptor protein 3 (NLRP3) inflammasome pathway, reduced levels of hydrogen sulfide (H2S) and sirtuin2 (SIRT2) activity. Endothelial specific knockout of cystathionine-γ-lyase (CSE) led to premature aging of blood vessels, and excessive activation of the SIRT2/NLRP3 inflammasome. Finally, H2S supplementation improved vascular and endothelial cell function, normalized inflammatory cytokine levels, and thereby reversed endothelial aging through SIRT2/NLRP3 mediated pathway. In this study, we found that the decrease in SIRT2 activity in aging endothelial cells increased the level of NLRP3 inflammasome and H2S inhibited inflammation to improve endothelial aging through the SIRT2/NLRP3 pathway. This provided H2S could be a new target for improving endothelial aging, and offered new strategies for defending human aging.