Hydrogen sulfide ameliorates senescence in vascular endothelial cells through ameliorating inflammation and activating PPARδ/SGLT2/STAT3 signaling pathway

Danyang Tian, Jinqi Meng, Lin Li, Hongmei Xue, Qi Geng, Yuxin Miao, Meng Xu, Ru Wang, Xiangjian Zhang, and Yuming Wu

Hydrogen sulfide (H2S) promotes anti-inflammatory molecules and inhibits pro-inflammatory cytokines in endothelial cells (ECs). The senescent ECs exhibit reduction of H2S, eNOS and PPARδ, coupled with increased inflammatory molecules, sodium glucose transporter type 2 (SGLT2) and phosphorylation of STAT3, which could be reversed by the administration of a slow but sustained release agent of H2S, GYY4137. Decreased production of eNOS and upregulated p-STAT3 and SGLT2 in senescent ECs are reversed by replenishment of SGLT2 inhibitor EMPA and PPARδ agonist GW501516. GYY4137, GW501516 and EMPA preserve the endo-thelial dependent relaxation (EDR) in D-gal treated aorta, while GSK0660 destroys the aortic relaxation even with the GYY4137 supplement. In a word, senescent ECs (wrinkled dolphins) manifest aggravated expressions of inflammatory molecules, and decreased production of CSE. H2S (bubbles) benefits against endothelial dysfunction through anti-inflammation effect of PPARδ/ SGLT2/p-STAT3 signaling pathway in senescent ECs and should be considered as a potential therapeutic target for anti-ageing treatment (young dolphins).

This cover is designed by Yinxi Zhou and Jianfeng Jin from Hainan Medical University.