Effects of a PPAR-gamma (Peroxisome Proliferator-Activated Receptor-gamma) Activator on Flow-Mediated Brachial Artery Dilation and Circulating Level of microRNA-21 in Hypertensive Type 2 Diabetic Patients.
10.5646/jksh.2013.19.4.99
- Author:
Ji Weon LEE
1
;
Soon Jun HONG
;
Han Saem JEONG
;
Hyung Joon JOO
;
Jae Hyoung PARK
;
Chul Min AHN
;
Cheol Woong YU
;
Do Sun LIM
Author Information
1. Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea. psyche94@hanmail.net
- Publication Type:Original Article ; Randomized Controlled Trial
- Keywords:
Pioglitazone;
MicroRNAs;
Diabetes mellitus;
Atherosclerosis
- MeSH:
Adiponectin;
Atherosclerosis;
Brachial Artery*;
C-Reactive Protein;
Coronary Artery Disease;
Cytokines;
Diabetes Mellitus;
Endothelial Cells;
Follow-Up Studies;
Heart Failure;
Humans;
Hyperlipidemias;
Hypertension;
Intercellular Adhesion Molecule-1;
Interleukin-6;
MicroRNAs;
Prevalence;
Prospective Studies;
Risk Factors;
Smoke;
Smoking;
Stroke;
Tumor Necrosis Factor-alpha;
Urinary Bladder Neoplasms;
Vascular Cell Adhesion Molecule-1
- From:Journal of the Korean Society of Hypertension
2013;19(4):99-111
- CountryRepublic of Korea
- Language:English
-
Abstract:
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-alpha (TNF-alpha), 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-alpha (-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-alpha, sICAM-1, and sVCAM-1.