Volume 109, Issue 2 , Pages 113-119, February 2010
Rosiglitazone Reduces Plasma Levels of Inflammatory and Hemostatic Biomarkers and Improves Global Endothelial Function in Habitual Heavy Smokers Without Diabetes Mellitus or Metabolic Syndrome
Article Outline
Background/Purpose
Thiazolidinediones have anti-atherothrombotic effects in diabetic patients. However, the effects of rosiglitazone on inflammatory and hemostatic markers, as well as global endothelial function in non-diabetic smokers are unknown.
Methods
Twenty-seven healthy male heavy smokers without metabolic syndrome were enrolled in this double-blind, controlled study. Fourteen subjects received 4 mg/day rosiglitazone for 8 weeks (group R) and 13 subjects received placebo (group C). Changes in the reflection index (ΔRI) of β-agonist-induced endothelium-dependent vasodilatation by photoplethysmography and plasma biomarkers were measured before and after treatment.
Results
Matrix metalloproteinase-9, fibrinogen, and high-sensitivity C-reactive protein were reduced significantly in group R after treatment as compared with the baseline [84.1 (45.6 139.0) vs. 123.9 (58.4 141.8) ng/mL, p = 0.03; 2914 (2400-3553) vs. 3220 (2542-3940) mg/L, p = 0.04; and 3.4 (2.2 5.1) vs. 5.5 (4.1 6.8) mg/L, p = 0.009, respectively]. ΔRI was improved markedly in group R as compared with the baseline [13.5 (4.2 65.1) vs. 2.5 (−10.6 to 9.3)%; p = 0.024]. These biomarkers and ΔRI did not differ significantly in the group C. There were no significant changes in fasting plasma glucose, insulin, homeostasis model assessment index, and lipid profile in both groups R and group C.
Conclusion
Rosiglitazone significantly reduces plasma levels of inflammatory and hemostatic biomarkers, and restores global endothelial dysfunction, independently from insulin sensitization, in healthy smokers.
Key Words: endothelium , metabolic syndrome , peroxisome proliferator-activated receptor , rosiglitazone , smoking
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References
- Rosiglitazone short-term monotherapy lowers fasting and post-prandial glucose in patients with type II diabetes . Diabetologia . 2000;43:278–284
- Non-hypoglycemic effects of thiazolidinediones . Ann Intern Med . 2001;134:61–71
- . Peroxisome prolifer-ator-activated receptor-gamma-mediated effects in the vasculature . Circ Res . 2008;102:283–294
- . Pioglitazone with sulfonylurea: glycemic and lipid effects in Taiwanese type 2 diabetic patients . Diabetes Res Clin Pract . 2005;70:193–194
- Effect of rosiglitazone treatment on nontraditional markers of cardiovascular disease in patients with type 2 diabetes melli-tus . Circulation . 2002;106:679–684
- Differential regulation by troglitazone of plasminogen activator inhibitor type 1 in human hepatic and vascular cells . J Clin Endocrinol Metab . 2000;85:1563–1568
- Antidiabetic PPARγ-activator rosiglitazone reduces MMP-9 serum levels in type 2 diabetic patients with coronary artery disease . Arterioscler Thromb Vasc Biol . 2003;23:283–288
- Platelet sarcoplasmic endoplasmic reticulum Ca2+-ATPase and mu-calpain activity are altered in type 2 diabetes mellitus and restored by rosiglitazone . Circulation . 2008;117:52–60
- Peroxisome proliferator-activated receptor gamma agonist improves arterial stiffness in patients with type 2 diabetes mellitus and coronary artery disease . Metabolism . 2007;56:1396–1401
- . Effect of thiazolidinedione therapy on restenosis after coronary stent implantation: a meta-analysis of randomized controlled trials . Am Heart J . 2007;154:144–150
- Oxidant stress impairs in vivo reendothelialization capacity of endothelial progenitor cells from patients with type 2 diabetes melli-tus: restoration by the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone . Circulation . 2007;116:163–173
- Rosiglitazone improves insulin sensitivity and lowers blood pressure in hypertensive patients . Diabetes Care . 2003;26:172–178
- Effects of rosiglitazone on endothelial function, C-reactive protein, and components of the metabolic syndrome in nondiabetic patients with the metabolic syndrome . Am J Cardiol . 2004;93:362–365
- Effect of rosiglita-zone on endothelial function and inflammatory markers in patients with the metabolic syndrome . Diabetes Care . 2006;29:1071–1076
- . Peroxisome proliferators-activated receptors (PPARs): nuclear receptors at the crossroads between lipid metabolism and inflammation . Inflamm Res . 2000;49:497–505
- Troglitazone has a scavenging effect on reactive oxygen species . Biochem Biophys Res Commun . 1997;235:113–116
- Troglitazone inhibits atherosclerosis in apolipoprotein E-knockout mice. Pleiotropic effects on CD36 expression and HDL . Arterioscler Thromb Vasc Biol . 2001;21:372–377
- Peroxisome proliferators-activated receptor γ ligands inhibit development of atherosclerosis in LDL receptor-deficient mice . J Clin Invest . 2000;106:523–531
- Pioglitazone, a peroxisome proliferators-activated receptor-γ agonist, attenuates left ventricular remodeling and failure after experimental myocardial infarction . Circulation . 2002;106:3126–3132
- Relative and absolute excess risks of coronary heart disease among women who smoke cigarettes . N Engl J Med . 1987;317:1303–1309
- Synergic effect of thrombomodulin promoter-33G/A polymorphism and smoking on the onset of acute myocardial infarction . Thromb Haemost . 2002;87:86–91
- Acute myocardial infarction in young and very old Chinese adults: clinical and therapeutic implications . Int J Cardiol . 1994;44:29–36
- . Long-term cigarette smoking impairs endothelium-dependent coronary artery vasodilator function . Circulation . 1995;92:1094–1100
- Lifetime smoking exposure affects the association of C-reactive protein with cardiovascular disease risk factors and subclinical disease in healthy elderly subjects . Arterioscler Thromb Vasc Biol . 1997;17:2167–2176
- . The influence of smoking on soluble adhesion molecules and endothelial cell markers . Thromb Res . 1997;85:433–438
- Cigarette smoking sensitizes and desensitizes impedance-measured ADP-induced platelet aggregation in whole blood . Thromb Haemost . 1995;74:730–735
- Effect of cigarette smoking on plasma metalloproteinase-9 concentration . Clin Chim Acta . 1998;276:173–177
- . Executive summary of the third report of the National Cholesterol Education Program (NECP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) . JAMA . 2001;285:2486–2497
- Effect of atrial fibrillation on pulmonary venous flow patterns assessed by Doppler transesophageal echocardiography . Chest . 2000;117:1546–1550
- Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man . Diabetologia . 1985;28:412–419
- Variability of flow mediated dilation: consequences for clinical application . Atherosclerosis . 2001;157:369–373
- Within-subject variability of flow-mediated vasodilation of the brachial artery in healthy men and women: implications for experimental studies . Ultrasound Med Biol . 2003;29:401–406
- Repeatability of noninvasive surrogates of endothelial function . Am J Cardiol . 2004;94:693–696
- Endothelial function is associated with pulse pressure, pulse wave velocity, and augmentation index in healthy humans . Hypertension . 2006;48:602–608
- Photoplethysmographic assessment of pulse wave reflection . J Am Coll Cardiol . 1999;34:2007–2014
- Assessment of endothelial function using peripheral waveform analysis. A clinical application . J Am Coll Cardiol . 2002;40:521–528
- Pulse wave analysis. Clinical evaluation of a noninvasive, widely applicable method for assessing endothelial function . Arterioscler Thromb Vasc Biol . 2002;22:147–152
- Oxidative stress could precede endothelial dysfunction and insulin resistance in Indian Mauritians with impaired glucose metabolism . Diabetologia . 2001;44:706–712
- Rapid effects of rosiglitazone treatment on endothelial function and inflammatory biomarkers . Arterioscler Thromb Vasc Biol . 2005;25:1804–1809
- . A rational approach to pathogenesis and treatment of type 2 diabetes mellitus, insulin resistance, inflammation, and atherosclerosis . Am J Cardiol . 2002;90:G27–G33
- The 161TT genotype in the exon 6 of peroxisome proliferator-activated receptor γ gene is associated with premature acute myocardial infarction and increased lipid peroxidation in habitual heavy smokers . Clin Sci . 2004;107:461–466
- Quantification of PPAR-gamma protein in monocyte/macrophages from healthy smokers and non-smokers: a possible direct effect of nicotine . Life Sci . 2007;81:906–915
- Cardiovascular outcomes in trials of oral diabetes medications: a systematic review . Arch Intern Med . 2008;168:2070–2080
- . Winners and losers at the rosiglitazone gamble. A meta-analytical approach at the definition of the cardiovascular risk profile of rosiglitazone . Diabetes Res Clin Pract . 2008;82:48–57
PII: S0929-6646(10)60031-9
doi:10.1016/S0929-6646(10)60031-9
© 2010 Formosan Medical Association & Elsevier. Published by Elsevier Inc. All rights reserved.
Volume 109, Issue 2 , Pages 113-119, February 2010
