Fig. 7.

HO-1 modulation of plaque characteristics in the murine TS model. a The figure depicts the summary timeline of the experiment. Tandem stenosis surgery was performed on ApoE-/- mice (6 weeks on western diet at 12 weeks of age). Cobalt protoporphyrin IX (CoPPIX, HO-1 inducer) and Zinc protoporphyrin IX (ZnPPIX, HO-1 inhibitor) were used for HO-1 enzyme modulation. Two weeks after the TS surgery, intraperitoneal injections of ZnPPIX or CoPPIX or the vehicle were performed every second day for 5 weeks (n = 8 in each group). The mice were killed after 5 weeks of injection for analysis of NIRAF, plaque burden and necrotic core. b Bar graph comparing mean fluorescence intensity ± SEM of unstable plaque segments in three groups of the TS model (vehicle alone, HO-1 inhibitor ZnPPIX, HO-1 inducer CoPPIX). There was a significantly higher fluorescence signal in unstable segments of the ZnPPIX group compared to the vehicle group as well as the CoPPIX group (p < 0.05, Kruskal–Wallis test followed by Dunn’s multiple comparisons test). c Bar graph demonstrating the plaque burden (mean cubic microliter ± SEM; one way ANOVA, left graph) and necrotic core (mean % of lesion area ± SEM; Kruskal–Wallis test followed by Dunn’s multiple comparisons test, right graph) in three different groups of the TS mouse model. The plaque burden and necrotic core in the ZnPPIX group were significantly higher than the other two groups. d Histological sections depicting the representative pictures of three different groups stained with Oil Red O. e Immunohistochemistry staining of glycophorin A and hemoglobin in the unstable plaques from three groups further confirmed the presence of red blood cells and hemoglobin. Scale bar indicates 1 mm in b and 100 µm in d and e