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Fig. 6 Validation of the association of SPTBN1 expression in human plaque and clinically relevant endpoints. A + B Validation of SPTBN1 expression in carotid artery plaque at mRNA (A) and protein level in the BIKE cohort (B), showing significant downregulation of SPTBN1 in plaque tissue compared to normal arteries or tissue adjacent to the plaque, respectively. To investigate the role of SPTBN1 in inflammation and vascular permeability in vivo, we assessed whether SPTBN1 expression is linked to intraplaque bleeding. C In the Maastricht Human Plaque Study cohort, sptbn1 expression showed an inverse correlation with the extent of intraplaque hemorrhage, here shown for one splicing variant (probe-1) (P = 0.0015; r2 = 0.2309). D In the independent Atheroexpress cohort, plaques of patients suffering from a cardiovascular event during follow-up had fourfold lower expression of SPTBN1 protein than event-free patients (E). In the same BIKE cohort, SPTBN1 mRNA expression was significantly lower in plaque of symptomatic vs asymptomatic patients. F The peptidomics dataset of the Maastricht Human Plaque Study was analyzed for peptides with significant correlation with module L; the corresponding protein list was strongly overrepresented in proteins of associated with hemorrhage (red) as well as proteins linked to ECM and endothelial cell adhesion (blue). Data are from n = 127 (A, E; BIKE), 36 (B; BIKE), 43 (C, F, Maastricht Human Plaque Study), and 28 (D; AtheroExpress) patient samples; error bars indicate SD; *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.005, ****p ≤ 0.001