| Literature DB >> 34294713 |
Meng-Lin Chao1, Shanshan Luo1, Chao Zhang1, Xuechun Zhou1, Miao Zhou1, Junyan Wang2, Chuiyu Kong1, Jiyu Chen1, Zhe Lin1, Xin Tang1, Shixiu Sun1, Xinlong Tang3,4, Hongshan Chen1, Hong Wang5, Dongjin Wang3,4, Jin-Peng Sun2,6, Yi Han7, Liping Xie8,9, Yong Ji10,11,12.
Abstract
Atherosclerosis-associated cardiovascular disease is one of the main causes of death and disability among patients with diabetes mellitus. However, little is known about the impact of S-nitrosylation in diabetes-accelerated atherosclerosis. Here, we show increased levels of S-nitrosylation of guanine nucleotide-binding protein G(i) subunit alpha-2 (SNO-GNAI2) at Cysteine 66 in coronary artery samples from diabetic patients with atherosclerosis, consistently with results from mice. Mechanistically, SNO-GNAI2 acted by coupling with CXCR5 to dephosphorylate the Hippo pathway kinase LATS1, thereby leading to nuclear translocation of YAP and promoting an inflammatory response in endothelial cells. Furthermore, Cys-mutant GNAI2 refractory to S-nitrosylation abrogated GNAI2-CXCR5 coupling, alleviated atherosclerosis in diabetic mice, restored Hippo activity, and reduced endothelial inflammation. In addition, we showed that melatonin treatment restored endothelial function and protected against diabetes-accelerated atherosclerosis by preventing GNAI2 S-nitrosylation. In conclusion, SNO-GNAI2 drives diabetes-accelerated atherosclerosis by coupling with CXCR5 and activating YAP-dependent endothelial inflammation, and reducing SNO-GNAI2 is an efficient strategy for alleviating diabetes-accelerated atherosclerosis.Entities:
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Year: 2021 PMID： 34294713 DOI： 10.1038/s41467-021-24736-y
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919