Effects of rosiglitazone on endothelial function, C-reactive protein, and components of the metabolic syndrome in nondiabetic patients with the metabolic syndrome

Wang, Tzung‐Dau; Chen, Wen‐Jone; Lin, Jong‐Wei; Chen, Ming-Fong; Lee, Yuan‐Teh

doi:10.1016/j.amjcard.2003.10.022

Cited by 142 publications

(81 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our finding that rosiglitazone did not raise HDL-C in patients with metabolic syndrome are consistent with the findings from 3 previous studies of patients without diabetes, 2 involving patients with coronary artery disease 11,16 and 1 involving nonobese patients with metabolic syndrome. 17 We found no effect of rosiglitazone on apoA-1 levels, but an increase in apoA-II levels. ApoA-II has been associated with visceral fat accumulation and impaired catabolism of large VLDL particles.…”

Section: Discussioncontrasting

confidence: 53%

“…Our observed 26% reduction in HOMA-IR with rosiglitazone is consistent with that found in previous studies in patients without diabetes. 16,17 The fasting glucose levels in the control group were higher at baseline than in the rosiglitazone group, and the comparable decrease in HOMA-IR in the control group may be attributable to the decrease in fasting glucose level in this group between baseline and follow-up, representing regression to the mean. There was no measurable change in weight, exercise, or other lifestyle that would otherwise have accounted for this change.…”

Section: Discussionmentioning

confidence: 94%

“…24 Rosiglitazone has been shown to lower CRP in nondiabetic patients with coronary artery disease 16 and in nonobese Taiwanese patients with metabolic syndrome. 17 The HDL effects of rosiglitazone differ from those of pioglitazone. The recently published GLAI study directly comparing rosiglitazone and pioglitazone in patients with diabetes showed a 14.9% increase in HDL-C with pioglitazone versus a 7.8% increase with rosiglitazone.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Effects of Rosiglitazone on Lipids, Adipokines, and Inflammatory Markers in Nondiabetic Patients With Low High-Density Lipoprotein Cholesterol and Metabolic Syndrome

Samaha

Szapary

Iqbal

et al. 2006

ATVB

126

View full text Add to dashboard Cite

Background-PPAR-␥ agonists improve insulin sensitivity and glycemic control in type 2 diabetes and may reduce atherosclerosis progression. Thus, PPAR-␥ agonists may be an effective therapy for metabolic syndrome. However, the full spectrum of potentially antiatherogenic mechanisms of PPAR-␥ agonists have not been fully tested in nondiabetic patients with metabolic syndrome. Methods and Results-We performed a prospective, double-blinded, placebo-controlled study of 60 nondiabetic subjects with low high-density lipoprotein cholesterol (HDL-C) level and metabolic syndrome to rosiglitazone 8 mg daily or placebo for 12 weeks. We found no significant effect of rosiglitazone on HDL-C (ϩ5.5% versus ϩ5.8%, Pϭ0.89), and an increase in total cholesterol (ϩ8% versus Ϫ1%; Pϭ0.03). Nevertheless, rosiglitazone significantly increased adiponectin (ϩ168% versus ϩ25%; PϽ0.001), and lowered resistin (Ϫ6% versus ϩ4%; Pϭ0.009), C-reactive protein (Ϫ32% versus ϩ36%, Pϭ0.002), interleukin (IL)-6 (Ϫ22% versus ϩ4%, PϽ0.001), and soluble tumor-necrosis factor-␣ receptor-2 (Ϫ5% versus ϩ7%, PϽ0.001). Conclusions-These findings suggest that rosiglitazone, presumably through its PPAR-␥ agonist properties, has direct effects on inflammatory markers and adipokines in the absence of favorable lipid effects. These findings may help explain the mechanism underlying the possible antiatherosclerotic effects of rosiglitazone.

show abstract

Section: Discussioncontrasting

confidence: 53%

Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of Rosiglitazone on Lipids, Adipokines, and Inflammatory Markers in Nondiabetic Patients With Low High-Density Lipoprotein Cholesterol and Metabolic Syndrome

Samaha

Szapary

Iqbal

et al. 2006

ATVB

126

View full text Add to dashboard Cite

show abstract

“…In addition, angiotensin II type 1 receptor blockade may activate peroxisome proliferator-activated receptor ␥ to directly induce adiponectin expression (51). The reduction in blood pressure observed in SHRs treated with rosiglitazone may be due to its effects to improve endothelial dysfunction by enhancing insulin-stimulated production of NO (52,53), decreasing ET-1 levels (54), and decreasing expression of angiotensin receptors (55). Because reduction of blood pressure in SHRs treated with rosiglitazone is accompanied by substantial reduction in serum ET-1 levels, lowering of basal levels of ET-1 (secondary to reduced fasting insulin levels and improved insulin sensitivity) may be an important mechanism by which rosiglitazone lowers blood pressure in SHRs.…”

Section: Discussionmentioning

confidence: 99%

Treatment of Spontaneously Hypertensive Rats With Rosiglitazone and/or Enalapril Restores Balance Between Vasodilator and Vasoconstrictor Actions of Insulin With Simultaneous Improvement in Hypertension and Insulin Resistance

et al. 2006

View full text Add to dashboard Cite

“…16 Nongenomic mechanisms that increase endothelial NO production 17 may explain emerging data from clinical studies indicating that PPAR-␥ ligands improve endothelial function in human subjects. 18 Finally, the mechanism of action of PPAR-␣ agonists described by Goya et al 3 has to be considered in relation to other therapies that potentially regulate the bioactivity of eNOS. eNOS is a tightly coupled enzyme system that may be easily dysregulated by perturbations in availability of substrates (eg, L-arginine) 19 and cofactors (eg, tetrahydrobiopterin), 20 as well as by competitive inhibitors such as increased concentrations of asymmetrical dimethyl-arginine (ADMA).…”

Section: See Page 658mentioning

confidence: 99%

Regulation of Endothelial Nitric Oxide Synthase by PPAR Agonists: Molecular and Clinical Perspectives

Watts

Staels

2004

ATVB

View full text Add to dashboard Cite

E ndothelial nitric oxide synthase (eNOS) is one of three NOS isoforms that catalyze the formation of nitric oxide (NO) and L-citrulline by the oxidation of the guanido-nitrogen group of L-arginine. The cardiovascular importance of this reaction relies on the formation of NO, a signaling molecule that regulates vascular tone, platelet aggregation, oxidative stress, leukocyte adherence, and smooth muscle cell mitogenesis. 1 Peroxisome proliferator-activated receptors (PPARs) are a subfamily of the nuclear receptor family of transcription factors that control the expression of key genes involved in the regulation of metabolism, inflammation, and thrombosis. 2 Transcriptional control involves ligand activation followed by either heterodimerization with a retinoid X receptor and binding to the promoter region of target genes, or a DNA-binding independent mechanism that interferes negatively with proinflammatory factor pathways. Of the three PPAR isoforms (␣, ␤/␦, and ␥), PPAR-␣ is expressed chiefly in fatty acid-oxidizing tissues including liver, skeletal muscle, and heart, but also in endothelial and vascular smooth muscle cells and macrophages within the arterial wall. Despite a plethora of basic research demonstrating that PPAR-␣ activation by synthetic ligands (eg, fibrates) has favorable antiatherogenic properties, 2 the corresponding effects on eNOS and the biology of NO has surprisingly not yet been explored. See page 658In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology, Goya et al 3 demonstrate for the first time that specific PPAR-␣ agonists, such as fenofibrate, regulate eNOS in cultured endothelial cells. Using classical molecular biology techniques and bovine aortic endothelial cells as a model, fenofibrate was shown to increase the mRNA expression, protein level, and enzyme activity of eNOS in a dosedependent manner at concentrations within the range of its EC 50 value for human PPAR␣. The authors found that the eNOS promoter sequence does not possess a PPAR response element and, accordingly, showed that fenofibrate did not enhance eNOS promoter activity. However, in mRNA stability assays, fenofibrate increased the half-life of eNOS mRNA. The observation that PPAR-␣ agonists stabilize mRNA levels is unusual and raises the question of whether these effects occur via PPAR-␣. Further studies employing in vitro gene knock-down technology and/or in vivo analysis on PPAR-␣-deficient mice are required to answer this important issue and to demonstrate the pathophysiological relevance of these findings. Goya et al 3 also present limited data indicating that the effect of fenofibrate on eNOS was shared by bezafibrate, a less specific PPAR-␣ agonist, but not rosiglitazone, a highly specific PPAR-␥ agonist.From a molecular perspective, these findings have to be placed within the context of the other antiatherogenic mechanisms of action of PPAR-␣ agonists 2 and the complexity of the regulation of eNOS. 4 PPAR-␣ is classically involved in the systemic regulation of lipid and lipoprotein metabolism b...

show abstract

Effects of rosiglitazone on endothelial function, C-reactive protein, and components of the metabolic syndrome in nondiabetic patients with the metabolic syndrome

Cited by 142 publications

References 17 publications

Effects of Rosiglitazone on Lipids, Adipokines, and Inflammatory Markers in Nondiabetic Patients With Low High-Density Lipoprotein Cholesterol and Metabolic Syndrome

Effects of Rosiglitazone on Lipids, Adipokines, and Inflammatory Markers in Nondiabetic Patients With Low High-Density Lipoprotein Cholesterol and Metabolic Syndrome

Treatment of Spontaneously Hypertensive Rats With Rosiglitazone and/or Enalapril Restores Balance Between Vasodilator and Vasoconstrictor Actions of Insulin With Simultaneous Improvement in Hypertension and Insulin Resistance

Regulation of Endothelial Nitric Oxide Synthase by PPAR Agonists: Molecular and Clinical Perspectives

Contact Info

Product

Resources

About