Hydrogen sulfide improves vascular endothelial function in hypertensive states through SIRT6 anti-inflammatory signaling

Hypertension is commonly accompanied by endothelial dysfunction, characterized by an imbalance between vasodilatation and constriction, increased levels of the proinflammatory factors interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1), and decreased nitric oxide (NO) bioavailability. Using an angiotensin II (Ang II)-induced endothelial dysfunction model, we show that treatment with the hydrogen sulfide (H₂S) donor GYY4137 significantly reverses Ang II-induced damage. GYY4137 restores sirtuin 6 (SIRT6) expression, suppresses inflammation, and improves vasodilatory function. Furthermore, endothelial-specific cystathionine-γ-lyase (CSE)-deficient mice exhibit inflammation and endothelial dysfunction in blood vessels, which is reversed by H₂S supplementation. Critically, SIRT6 inhibitors block the protective effects of H₂S in the endothelium. This study demonstrates that H₂S protects vascular endothelial function by activating the SIRT6 anti-inflammatory pathway.