Peroxisome Proliferator-Activated Receptor Gamma(PPAR-gamma) Agonist Improves Endothelial Function in Diabetic Patients with Metabolic Syndrome: Pivotal Role of NOx and Inflammation

ABSTRACT

BACKGROUND AND OBJECTIVES: Nitric oxide (NO) is thought to have antiatherosclerotic properties. On the other hand, NO activity is reduced in patients with metabolic syndrome, and endothelial dysfunction is an important early sign of atherosclerosis in patients with metabolic syndrome. The aim of this study was to investigate the effect of pioglitazone on the endothelial function in terms of the plasma NOx (combined nitrate/nitrite), the circulating inflammatory markers and the autonomic nervous system. SUBJECTS AND METHODS: We randomized 40 subjects with metabolic syndrome, and they were assigned to receive 15 mg of pioglitazone per day (the PIO group, n=21) during 12 weeks or they were placed in the placebo group (the PLA group, n=19). We estimate the endothelial function by performing vascular ultrasound. The plasma NOx levels, the levels of the inflammatory markers and the GRK2 levels were measured. RESULTS: After 12 weeks of therapy, flow mediated dilation (FMD) was improved in the PIO group (from 6.7+/-6% to 11.7+/-5%, respectively p<0.05), but not in the PLA group. The level of plasma NOx was increased in the PIO group (from 67.7+/-30 nmol/dL to 92.9+/-41 nmol/dL, respectively p<0.001), but not in the PLA group. The plasma levels of hsCRP and IL-6 dropped significantly (from 2.6+/-2.3 mg/L to 1.2+/-1.3 mg/L and 1.7+/-2.1 pg/mL to 0.7+/-0.5 pg/mL, respectively p<0.05) in the PIO group, but not in the PLA group. The levels of GRK2 (the PLA group from 0.0061+/-0.0023 ng to 0.0075+/-0.0031 ng, and the PIO group from 0.0024+/-0.002 ng to 0.0015+/-0.001 ng, p=ns) didn't dropped significantly. CONCLUSION: Administration of PPAR-gamma agonist in patients suffering with metabolic syndrome improves their endothelial function, enhances the production of NOx and reduces the proinflammatory markers, but this is not related to sympathetic regulation. PPAR-gamma agonist may be able to modulate the progression of atherosclerosis.