Abstract 266: Differential Vascular and Metabolic Effects of PPAR3 Activation with Pioglitazone in Hypertensive and Hypercholesterolemic Patients
PPARγ controls major metabolic, inflammatory, and vascular processes involved in the initiation, progression and complications of atherosclerosis. Thiazolidinediones exert pleiotropic effects also in non-diabetic patients with atherosclerotic risk factors. Whether these actions are modulated by the pathophysiological milieu underlying each specific risk factor is unknown. We tested the hypothesis that the effects of PPARγ activation with pioglitazone differ between non-diabetic patients with hypertension and hypercholesterolemia. Methods. Forty hypertensive and 40 hypercholesterolemic patients were enrolled in double-blind, placebo controlled, cross-over study. In each treatment phase, patients received either pioglitazone 45 mg daily or placebo for 8 weeks. Endothelial function (forearm plethysmography) and laboratory tests were performed at the end of each 8-week period. Results. Pioglitazone lowered insulin and improved QUICKI in both groups (P<0.01). In hypercholesterolemics, pioglitazone increased HDL (P=0.002) and decreased triglycerides (P=0.001), non-HDL cholesterol (P<0.02), and free fatty acids (P<0.001). Only HDL was increased in hypertensives (P=0.007). CRP was reduced in hypercholesterolemics (P=0.01). Pioglitazone increased adiponectin in both groups (P<0.0001), while resistin was decreased only in hypertensives (P=0.005). Changes in resistin correlated with variations in insulin (r=0.45, P<0.01). No significant difference was noted in the improvement of the vasodilatory response to bradykinin between the two groups. Changes in total cholesterol were the only predictors of improved endothelial reactivity in the hypercholesterolemic group. Conclusions. In non-diabetic patients with hypertension or hypercholesterolemia, treatment with pioglitazone exerts multiple vascular, metabolic, and anti-inflammatory effects. However these actions differ between hypertensive and hypercholesterolemic patients. Our results suggest that the effects of PPARγ activation in non-diabetic patients are modulated by the specific underlying pathophysiological milieu, and may serve as the basis for further investigations on the therapeutic potential of PPARγ agonists in the treatment of atherosclerosis.