KMID : 0648320130190040099
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Journal of The Korean Society of Hypertension 2013 Volume.19 No. 4 p.99 ~ p.111
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Effects of a PPAR-¥ã (Peroxisome Proliferator-Activated Receptor-gamma) Activator on Flow-Mediated Brachial Artery Dilation and Circulating Level of microRNA-21 in Hypertensive Type 2 Diabetic Patients
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Lee Ji-Weon
Hong Soon-Jun Jeong Han-Saem Joo Hyung-Joon Park Jae-Hyoung Ahn Chul-Min Yu Cheol-Woong Lim Do-Sun
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Abstract
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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-¥á (TNF-¥á), 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 ¡¾ 0.34 mm vs. 0.02 ¡¾ 0.25 mm, p £¼0.05, respectively) and in the level of circulating microRNA-21 (0.23 ¡¾ 0.05 vs. -0.06 ¡¾ 0.04, p £¼0.05, 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 ¡¾ 2.32 pg/mL vs. -1.34 ¡¾ 2.12 pg/mL, p £¼ 0.05, respectively), TNF-¥á (-1.54 ¡¾ 1.51 pg/mL vs. 0.14 ¡¾ 1.12 pg/mL, p £¼ 0.05, respectively), sICAM-1 (-39 ¡¾ 52 ng/mL vs. 6 ¡¾ 72 ng/mL, p £¼0.05, respectively), and sVCAM-1 (-154 ¡¾ 198 ng/mL vs. -11 ¡¾ 356 ng/mL, p £¼ 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-¥á, sICAM-1, and sVCAM-1.
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KEYWORD
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Pioglitazone, MicroRNAs, Diabetes mellitus, Atherosclerosis
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