Fig. 3: Inhibition of SNO-GNAI2 at Cys66 mitigates endothelial dysfunction in diabetes-accelerated atherosclerosis.
LDLr−/− mice were transfected with AAVendo-GFP, AAVendo-GNAI2-WT, or AAVendo-GNAI2-C66A, respectively, and randomly separated into NC, HFD, and STZ + HFD groups. a AAVendo-GNAI2-C66A significantly diminishes S-nitrosylation of GNAI2 in the aorta, as determined through a biotin-switch assay. n = 6 mice for each group. N.D represents no detected. b Endothelial specific transfection of GNAI2-C66A alleviates diabetes-accelerated atherosclerosis. Scale bar = 5 mm. n = 6 mice for each group. N.D represents no detected. c Endothelial specific transfection of GNAI2-C66A decreases plaque areas in the aortic roots, evidenced by hematoxylin and eosin staining (H&E). Scale bar = 200 μm. n = 6 mice for each group. N.D represents no detected. d, e AAVendo-GNAI2-C66A increases the stability of atherosclerotic plaques, as evidenced by picrosirius red staining for collagen (Scale bar = 200 μm), α-SMA for smooth muscle cells (Scale bar = 50 μm), CD68 for macrophage infiltration (Scale bar = 50 μm), and Oil Red O staining for lipid deposition (Scale bar = 200 μm), n = 6 mice for each group. N.D represents no detected. f Endothelial specific transfection of GNAI2-C66A rescues the impairment in endothelium-dependent relaxation induced by STZ and HFD in the presence of Ach (10−9 to 10−5 mol/L). n = 6 mice for each group. g The mRNA expressions of adhesion molecules (Icam1, Vcam1, Sele, and Selp) and chemokines (Cxcl1, Cxcl4, Ccl2, and Ccl5) are significantly reduced in aortas of STZ and HFD-treated LDLr−/− mice transfected with AAVendo-GNAI2-C66A. n = 6 mice for each group. Data are represented as the Mean ± SEM. a, b, e, f, g Welch ANOVA followed by Tamhane’s T2 test for post-hoc comparisons. c One-way ANOVA followed by Tukey’s test for post-hoc comparisons. Source data are provided as a Source Data file.
