Relation of Improvement in Endothelium-Dependent Flow-Mediated Vasodilation After Rosiglitazone to Changes in Asymmetric Dimethylarginine, Endothelin-1, and C-Reactive Protein in Nondiabetic Patients With the Metabolic Syndrome
Journal
American Journal of Cardiology
Journal Volume
98
Journal Issue
8
Pages
1057-1062
Date Issued
2006
Author(s)
Abstract
The mechanisms by which thiazolidinediones exert beneficial effects on the endothelium are still not clear. We examined the effects of rosiglitazone on the plasma markers of metabolic control (glucose, insulin, adiponectin, resistin, and lipid profiles), markers of inflammation (high-sensitivity C-reactive protein [CRP], interleukin-6, soluble CD40 ligand, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1), and markers of vasoreactivity (asymmetric dimethylarginine [ADMA] and endothelin-1) and analyzed the relations between changes in endothelium-dependent flow-mediated dilation of the brachial artery and changes in these markers to elucidate their roles in mediating the vascular protective effects of rosiglitazone. Of 70 nondiabetic patients who met a modified National Cholesterol Education Program definition of the metabolic syndrome, 35 were randomized to receive rosiglitazone (4 mg/day) and 35 to receive placebo for 8 weeks. At study end, treatment with rosiglitazone had significantly reduced plasma insulin (-25%, p = 0.004) and resistin (-16%, p <0.001), increased adiponectin (164%, p <0.001), low-density lipoprotein cholesterol (16%, p = 0.005), and apolipoprotein-B (14%, p = 0.003), and decreased CRP (-30%, p = 0.005), soluble CD40 ligand (-20%, p = 0.014), ADMA (-16%, p <0.001), and endothelin-1 (-11%, p <0.001) concentrations and systolic and diastolic blood pressures. Rosiglitazone treatment significantly improved flow-mediated dilation (p <0.001) and nitroglycerin-induced vasodilation (p = 0.001) of the right brachial artery. On multivariate analysis, changes in ADMA, endothelin-1, and CRP were independent predictors of improved endothelial reactivity with rosiglitazone. In conclusion, we have, for the first time, demonstrated the independent associations between the improvement in flow-mediated dilation and reductions in ADMA, endothelin-1, and CRP after 8 weeks of treatment with rosiglitazone in nondiabetic patients with the metabolic syndrome. These findings suggest that decreases in ADMA, endothelin-1, and CRP may serve as possible mechanisms for the improvement in endothelial function conferred by rosiglitazone treatment. ? 2006 Elsevier Inc. All rights reserved.
SDGs
Other Subjects
adiponectin; apolipoprotein B; biological marker; C reactive protein; CD40 ligand; endothelin 1; glucose; glyceryl trinitrate; insulin; intercellular adhesion molecule 1; interleukin 6; lipid; low density lipoprotein cholesterol; n(g),n(g) dimethylarginine; placebo; resistin; rosiglitazone; vascular cell adhesion molecule 1; adult; aged; artery dilatation; article; blood vessel reactivity; brachial artery; clinical article; clinical trial; concentration (parameters); controlled clinical trial; controlled study; diabetes mellitus; diastolic blood pressure; disease marker; double blind procedure; endothelium; female; human; insulin blood level; male; metabolic regulation; metabolic syndrome X; multivariate analysis; priority journal; protein blood level; systolic blood pressure; vasodilatation; Arginine; Blood Pressure; Body Mass Index; C-Reactive Protein; Case-Control Studies; Cholesterol, HDL; Endothelin-1; Endothelium-Dependent Relaxing Factors; Female; Glucose; Humans; Insulin; Male; Metabolic Syndrome X; Middle Aged; Regression Analysis; Thiazolidinediones; Treatment Outcome; Vasodilator Agents
Type
journal article