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

作　　者：Danyang Tian Jinqi Meng Lin Li Hongmei Xue Qi Geng Yuxin Miao Meng Xu Ru Wang Xiangjian Zhang Yuming Wu 

机构地区：[1]Department of Physiology,Hebei Medical University,Shijiazhuang 050017,China [2]Department of Sports,Hebei Medical University,Shijiazhuang 050017,China [3]College of Pharmacy,Hebei Medical University,Shijiazhuang 050017,China [4]Hebei Key Lab of Laboratory Animal Science,Hebei Medical University,Shijiazhuang 050017,China [5]Hebei Collaborative Innovation Center for Cardio-Cerebrovascular Disease,Shijiazhuang 050017,China [6]The Key Laboratory of Neural and Vascular Biology,Ministry of Education,Shijiazhuang 050017,China [7]Department of Pharmacology,Tianjin Key Laboratory of Inflammatory Biology,School of Basic Medical Sciences,Tianjin Medical University,Tianjin 300070,China

出　　处：《Acta Biochimica et Biophysica Sinica》2023年第9期1358-1369,共12页生物化学与生物物理学报（英文版）

基　　金：supported by the grants from the National Natural Science Foundation of China(Nos.91849120,32271155,and 31871154);the Natural Science Foundation of Hebei Province of China(No.C2020206025);the Funding Project for the Returned Overseas Scholars of Hebei Province(No.C20210342);the Youth Program in Higher Institutions of Hebei Province(No.QN2022126);the Supporting Program for Youth Technological Talents in Natural and Scientific Field in Hebei Medical University(Nos.CYQD2021006,TJZR202101).

摘　　要：Mounting evidence demonstrates that hydrogen sulfide(H2S)promotes anti-inflammatory molecules and inhibits pro-inflammatory cytokines in endothelial cells(ECs).This study aims to investigate the favorable action of H2S on endothelial function in senescence by inhibiting the production of inflammatory molecules.Senescent ECs exhibit a reduction in H2S,endothelial nitric oxide synthase(eNOS)and peroxisome proliferator-activated receptorδ(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 levels in senescent ECs are reversed by replenishment of the SGLT2 inhibitor EMPA and the PPARδagonist GW501516.The PPARδantagonist GSK0660 attenuates eNOS expression and increases the production of p-STAT3 and SGLT2.However,supplementation with GYY4137 has no beneficial effect on GSK0660-treated ECs.GYY4137,GW501516 and EMPA preserve endothelialdependent relaxation(EDR)in D-gal-treated aortae,while GSK0660 destroys aortic relaxation even with GYY4137 supplementation.In summary,senescent ECs manifest aggravated the expressions of the inflammatory molecules SGLT2 and p-STAT3 and decreased the productions of PPARδ,eNOS and CSE.H2S ameliorates endothelial dysfunction through the anti-inflammatory effect of the PPARδ/SGLT2/p-STAT3 signaling pathway in senescent ECs and may be a potential therapeutic target for anti-ageing treatment.

关 键 词：hydrogen sulfide endothelial cells INFLAMMATION SENESCENCE peroxisome proliferator-activated receptorδ 

分 类 号：R73[医药卫生—肿瘤]