Plaque Thrombosis is Reduced by Attenuating Plaque Inflammation with Pioglitazone and is Evaluated by Fluorodeoxyglucose Positron Emission Tomography.

INTRODUCTION: The relationship between the beneficial effects of pioglitazone in reducing clinical events and plaque inflammatory burden remains unknown. This study aimed to determine whether pioglitazone can reduce the number of plaque thrombosis incidences and whether decreasing plaque inflammation is the mechanism by which pioglitazone reduces plaque thromboses. METHODS AND RESULTS: therosclerotic rabbits were divided into two groups: the atherosclerosis group (n = 13) and pioglitazone group (n = 10). The rabbits underwent pharmacological triggering to induce thrombosis. Serum inflammatory markers, FDG uptake, macrophage, and neovessel staining detected arterial inflammation. PET/CT scans were performed twice (baseline and posttreatment scans). Plaque area, macrophages, and neovessels were measured and the histologic sections were matched with the PET/CT scans. Serum MMP-9 and hsCRP were lower in the pioglitazone group compared to the atherosclerosis group. The SUVmean significantly decreased in the pioglitazone group (0.62 ± 0.21 vs. 0.55 ± 0.19, P = 0.008), but increased in the atherosclerosis group (0.61 ± 0.15 vs. 0.91 ± 0.20, P < 0.000). The incidence rate of plaque rupture, plaque area, macrophage density, and neovessel density was significantly lower in rabbits with pioglitazone than without (15% vs. 38%, P < 0.001; 18.00 ± 2.30 vs. 27.00 ± 1.60; P < 0.001; 8.80 ± 3.94 vs. 28.26 ± 2.49; P < 0.001; 16.50 ± 3.09 vs. 29.00 ± 2.11; P < 0.001, respectively). Moreover, plaque area and macrophage density were positively correlated with SUV values. CONCLUSIONS: Our study suggests that pioglitazone can reduce the number of plaque thrombosis incidences by decreasing plaque inflammation. (18)F-FDG-PET/CT can detect plaque inflammation and assess the effects of antiatherosclerotic drugs.