Figure 4. Atherosclerosis severity is associated with decreased responsiveness of plaque macrophages to Wnt signaling in mice and humans.

(A–C) Cumulative expression of genes associated with the GO term GO:0016055 of data from Lin et al., 2019 represented in (A) Louvain clusters for both progression and resolution groups and (B) divided by treatment. (C) Individual GO:0016055 gene expression per cluster, comparing treatment groups. Red, higher expression in resolution; blue, higher expression in progression. (D) Human plaque macrophages obtained from endarterectomies (from Fernandez et al., 2019) were examined for their expression of the top 10 most upregulated genes from GO:0016055 in mouse resolving plaque macrophages (from Lin et al., 2019). Relative expression of symptomatic (Sym) versus asymptomatic (Asym) is presented. Permutation tests of Fernandez et al. expressed genes was performed to calculate the probability of 7 or more genes out of 10 to have lower expression in the Sym group, p=0.008. (E) Expression of seven Wnt marker genes (Axin2, Ddx3x, Wls, Senp2, Ctnnb1, Csnk1a1, and Amfr) was measured in peripheral blood mononuclear cells (PBMCs) from statin-naïve patients at presentation of acute coronary syndrome and 3 months intensive atorvastatin treatment follow-up (Alkhalil et al., 2018). (F) Change in the expression of the Wnt hallmark gene, Axin2, in PBMCs obtained from patients was examined in relation to change in plaque volume from presentation to follow-up (Alkhalil et al., 2018).