Figure 4: Semaglutide Affected Local (Aortic) and Systemic Inflammation

(A) Principal component analysis illustrates the total variance of the 275 genes analyzed. (B) Venn diagram of significant gene expression changes (60 μg/kg vs. vehicle; FDR = 5%) in LDLr−/− and ApoE−/− models. (C) Directions (activation z-scores) are shown for significant changes in represented pathways of IPA. (D) Gene expression changes by WD and semaglutide (compared to vehicle-dosed chow-fed animals), exemplifying genes that represent pathways with well described relevance to plaque formation and the pathophysiology of atherosclerosis. Benjamini-Hochberg-corrected p values: ****p < 0.0001; ***p < 0.001; **p < 0.01; *p < 0.05 versus LDLr−/−, WD; ####p < 0.0001, ###p < 0.001; ##p < 0.01; #p < 0.05 versus ApoE−/−, WD (uncorrected and Benjamini-Hochberg-corrected p values can be found in Supplemental Table S3). Subcutaneous administration of semaglutide in an LPS inflammation model reduced plasma levels of (E) TNFα: **p = 0.0024 versus vehicle at 1 h and p = 0.048 versus vehicle at 4 h, (F) IFNg: ** p = 0.0050 versus vehicle at 4 h, and (G) OPN: **p = 0.0014 versus vehicle at 4 h. FDR = false discovery rate; IPA = ingenuity pathway analysis; LPS = lipopolysaccharide; OPN = osteopontin; other abbreviations as in Figure 1.

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