J Korean Soc Hypertens.  2013 Dec;19(4):99-111. 10.5646/jksh.2013.19.4.99.

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

Affiliations
  • 1Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea. psyche94@hanmail.net

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.

Keyword

Pioglitazone; MicroRNAs; Diabetes mellitus; Atherosclerosis

MeSH Terms

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
Adiponectin
C-Reactive Protein
Cytokines
Intercellular Adhesion Molecule-1
Interleukin-6
MicroRNAs
Smoke
Tumor Necrosis Factor-alpha
Vascular Cell Adhesion Molecule-1
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