Effects of a PPAR- (Peroxisome γ Proliferator-Activated Receptor-gamma) Activator on Flow-Mediated Brachial Artery Dilation and Circulating Level of microRNA-21 in Hypertensive Type 2 Diabetic Patientss

초록

Background: Endothelial dysfunction has been documented in patients with type 2 diabetes especially when combined with hypertension. We prospectively investigated the effects of pioglitazone in improving endothelial function in hypertensive type 2 diabetic patients during the 6-month follow-up. Methods: Hypertensive type 2 diabetic patients were randomly assigned to pioglitazone (n = 25) or placebo (n = 25). Primary endpoint was to compare changes in brachial artery flow-mediated dilation (baFMD) between the 2 groups during the 6-month follow-up. Secondary endpoints were to compare changes in the circulating levels of microRNA-17, -21, 92a, -126, and -145 which have been known as indicators of endothelial cell migration and atherosclerosis progression during the 6-month follow-up. Inflammatory markers such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), high-sensitive C-reactive protein, adiponectin, soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) were compared during the follow-up. Results: The prevalences of risk factors such as hyperlipidemia, smoking, stroke, and family history of coronary artery disease did not show significant differences between the 2 groups. Increases in baFMD (0.33 ± 0.34 mm vs. 0.02 ± 0.25 mm, p ＜0.05, respectively) and in the level of circulating microRNA-21 (0.23 ± 0.05 vs. -0.06 ± 0.04, p ＜0.05, respectively) were significantly greater in the pioglitazone group when compared to the placebo group during the 6-month follow-up. No significant differences in the prevalences of new onset heart failure, fracture, and bladder cancer were noted during the follow-up between the 2 groups. Decreases in the levels of inflammatory marker such as IL-6 (-2.54 ± 2.32 pg/mL vs. -1.34 ± 2.12 pg/mL, p ＜ 0.05, respectively), TNF-α (-1.54 ± 1.51 pg/mL vs. 0.14 ± 1.12 pg/mL, p ＜ 0.05, respectively), sICAM-1 (-39 ± 52 ng/mL vs. 6 ± 72 ng/mL, p ＜0.05, respectively), and sVCAM-1 (-154 ± 198 ng/mL vs. -11 ± 356 ng/mL, p ＜ 0.05, respectively) were significantly greater in the pioglitazone group compared to the placebo group during the follow-up. Conclusions: In hypertensive type 2 diabetic patients, pioglitazone may increase baFMD and circulatory microRNA-21 and decrease inflammatory cytokines including IL-6, TNF-α, sICAM-1, and sVCAM-1.

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