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

作者：Fan Lu, Xueyuan Qin, Shanshan Lu, Jie Wan, Yuxin Miao, Xu Teng, Sheng Jin, Lin Xiao, Hongmei Xue, Qi Guo, Danyang Tian, Yin Wu · 发表于：Acta Biochimica et Biophysica Sinica · 年份：2025 · DOI：10.3724/abbs.2025221 · 研究领域：Sulfur Compounds in Biology、Sirtuins and Resveratrol in Medicine、Edible Oils Quality and Analysis

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.