Fig. 8: Graphic model of SNO-GNAI2-induced diabetes-accelerated atherosclerosis.

During diabetes-accelerated atherosclerosis, high glucose, and oxLDL increases S-nitrosylation of GNAI2 in endothelial cells, which enhances coupling with CXCR5 and reduces cAMP level. The reduction in cAMP dephosphorylates LATS1 and YAP, promotes nuclear translocation of YAP and promotes transcription of adhesion molecules and chemokines, which enhances endothelial inflammation. Melatonin restores phosphorylation of LAST1 and YAP through reducing iNOS-induced SNO-GNAI2 and alleviates endothelial inflammation, which improves diabetes-accelerated atherosclerosis. oxLDL oxidized low-density lipoprotein, GNAI2 guanine nucleotide-binding protein G(i) subunit alpha-2, CXCR5 C-X-C chemokine receptor type 5, cAMP cyclic adenosine monophosphate, LATS1 large tumor suppressor kinase 1, YAP Yes-associated protein, iNOS inducible nitric oxide synthase.