Troglitazone increases the resistance of low density lipoprotein to oxidation in healthy volunteers

Cominacini, Luciano; Young, Melissa; Capriati, Angela; Garbin, Ulisse; Pasini, Anna Fratta; Campagnola, M.; Davoli, A.; Rigoni, Annamaria; Contessi, G. B.; Cascio, Vincenzo Lo

doi:10.1007/s001250050809

Cited by 43 publications

(18 citation statements)

References 40 publications

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“…This is consistent with previous findings that have shown that TZD treatment of nondiabetic subjects does not have an effect on glucose metabolism. 23 In addition, we did not find changes in total cholesterol, HDL cholesterol, or triglyceride levels, making it unlikely that the effect on neointima formation resulted from changes in the lipid profile. Still, we did not perform oral glucose tolerance tests in our patients and cannot exclude the possibility that some of the patients might have had impaired glucose tolerance, which may have been influenced by pio treatment.…”

Section: Discussionmentioning

confidence: 62%

Pioglitazone Reduces Neointima Volume After Coronary Stent Implantation

et al. 2005

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Background-Restenosis requiring reintervention limits the long-term success after coronary stent implantation.Thiazolidinediones, like pioglitazone or rosiglitazone, are oral antidiabetic drugs with additional antirestenotic properties. In a randomized, placebo-controlled, double-blind trial, we examined the effect of 6-month pioglitazone therapy on neointima volume after coronary stenting in nondiabetic coronary artery disease patients. Methods and Results-Fifty nondiabetic patients after coronary stent implantation were randomly assigned to pioglitazone (30 mg daily; pio) or placebo (control) treatment in addition to standard therapy, and neointima volume was assessed by intravascular ultrasound at the 6-month follow-up. Both groups were comparable with regard to baseline characteristics, angiographic lesion morphology, target vessel, and length of the stented segment. In addition, there were no statistical differences in minimal lumen diameter before and after intervention, as well as reference diameter after stent implantation. In this study population of nondiabetic patients, pio treatment did not significantly change fasting blood glucose, fasting insulin, or glycosylated hemoglobin levels, as well as lipid parameters. In contrast, pio treatment significantly reduced neointima volume within the stented segment, with 2.3Ϯ1.1 mm 3 /mm in the pio group versus 3.1Ϯ1.6 mm 3 /mm in controls (Pϭ0.04). Total plaque volume (adventitia-lumen area) was significantly lower at follow-up in the pio group (11.2Ϯ3.2 mm 3 /mm) compared with controls (13.2Ϯ4.2 mm 3 /mm; Pϭ0.04). Moreover, the binary restenosis rate was 3.4% in the pio group versus 32.3% in controls (PϽ0.01). Conclusions-Thus, 6-month treatment with pio significantly reduced neointima volume after coronary stent implantation in nondiabetic patients. These data bolster the hypothesis that antidiabetic thiazolidinediones, in addition to their metabolic effects, exhibit direct antirestenotic effects in the vasculature.

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Section: Discussionmentioning

confidence: 62%

Pioglitazone Reduces Neointima Volume After Coronary Stent Implantation

et al. 2005

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“…This is consistent with previous findings showing that short-term TZD treatment of healthy subjects does not have an effect on glucose metabolism. 25 In addition, rosiglitazone treatment did not significantly alter total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels, although there was a slight increase in total cholesterol and triglycerides. In a larger population, these changes may have reached statistical significance, but because these effects would not be vasculoprotective, it is unlikely that improved endothelial function results from changes in the lipid profile.…”

Section: Discussionmentioning

confidence: 87%

Rapid Effects of Rosiglitazone Treatment on Endothelial Function and Inflammatory Biomarkers

Hetzel

Balletshofer

Rittig

et al. 2005

ATVB

133

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Background— Antidiabetic thiazolidinediones (TZDs), like rosiglitazone or pioglitazone, improve endothelial function in patients with type 2 diabetes or metabolic syndrome, but it is currently unknown, whether these beneficial effects of TZDs depend on their metabolic action or may be caused by direct effects on the endothelium. Therefore, the present study examined whether short-term rosiglitazone treatment influences endothelium-dependent vasodilation as well as serum levels of vascular disease biomarkers in healthy, nondiabetic subjects. Methods and Results— Short-term treatment (21 days) of healthy subjects (n=10) did not significantly change blood glucose levels or lipid profile. In contrast, rosiglitazone significantly increased flow-mediated, endothelium-dependent vasodilation already within the first day from 5.3±2.7% at baseline to 7.8±2.6%, further increasing it to 9.4±3.0% at day 21. In addition, the early improvement of endothelium-dependent vasodilation was paralleled by a rapid reduction of serum levels of the biomarkers C-reactive protein (CRP), serum amyloid A (SAA), and sE-selectin. Moreover, after drug withdrawal all markers remained suppressed for the whole follow-up period of 7 days. In contrast, rosiglitazone treatment did not significantly affect tumor necrosis factor (TNF)-α, interleukin (IL)-6, sICAM-1, sVCAM-1, and sCD40L levels. Conclusions— Our study suggests a direct effect of TZD treatment on endothelial function and inflammatory biomarkers of arteriosclerosis, promoting the concept that TZDs, independent of their metabolic action, may exhibit protective effects in the vessel wall.

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“…Since troglitazone is reported to have antioxidant properties, 22,23 its effect on NF-B activity was compared with 2 antioxidants, N-acetylcysteine (NAC) and pyrrolidine dithiocarbamate (PDTC), which have been shown to prevent NF-B activation. 24,25 IL-1 either alone or in combination with IFN markedly induced NF-B activity, though IFN by itself did not show any effects.…”

Section: Resultsmentioning

confidence: 99%

Troglitazone Upregulates Nitric Oxide Synthesis in Vascular Smooth Muscle Cells

Hattori

Kasai

1999

Hypertension

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Abstract-We investigated the effects of troglitazone on cytokine-stimulated nitric oxide (NO) production in cultured rat vascular smooth muscle cells (VSMC). The increase in NO formation caused by interleukin-1␣ (IL-1) was enhanced by troglitazone in a concentration-dependent manner. Bacterial lipopolysaccharide-stimulated NO synthesis was also increased by troglitazone. The combinations of IL-1, tumor necrosis factor-␣, or lipopolysaccharide with interferon-␥ (IFN) were strong stimuli for induction of NO synthesis in VSMC, which were further potentiated by the presence of troglitazone. When troglitazone was added at increasing intervals after the stimulation of VSMC with IL-1, the enhancement in NO production decreased as the interval lengthened, suggesting that troglitazone alters NO synthase (NOS) expression by VSMC rather than having a direct affect on VSMC NOS activity. Troglitazone had no effect on IL-1-elicited or IL-1/IFN-elicited nuclear factor-B activity in VSMC. Troglitazone inhibited the degradation of cytokine-induced NOS mRNA. Thus troglitazone appears to enhance IL-1-induced NOS mRNA levels by prolonging its half-life rather than activating its transcription, which is nuclear factor -B-dependent. No expression of peroxisome proliferator-activated receptor-␥ (PPAR␥) was detected in VSMC, and 15-deoxy-D 12,14 prostaglandin J 2 , the natural ligand for the PPAR␥, did not resemble the effect of troglitazone on IL-1-induced NO synthesis. These results indicate that troglitazone upregulates cytokine-stimulated NO synthesis in VSMC through PPAR␥-independent mechanisms. Considering its inhibitory effects on the action of numerous growth factors on VSMC, the direct vascular effects of troglitazone shown in this study may have important implications for prevention of restenosis and possibly atherosclerosis. (Hypertension. 1999;33:943-948.) Key Words: troglitazone Ⅲ nitric oxide Ⅲ peroxisome proliferator-activated receptor-␥ Ⅲ cytokines Ⅲ muscle, smooth, vascular T he thiazolidinediones are novel insulin-sensitizing agents that have been shown to significantly reduce hyperinsulinemia in insulin-resistant animals and humans and to reduce hyperglycemia in diabetic models, including humans. [1][2][3] Migration and proliferation of vascular smooth muscle cells (VSMC) are critical events in the development of restenosis and in the progression of atherosclerosis. 4 A previous study demonstrated that the thiazolidinedione analogue pioglitazone inhibited insulin, epidermal growth factor, and serum-induced growth of cultured arterial VSMC. 5 The effect of troglitazone has been investigated on intimal hyperplasia after balloon injury of the vessel wall, a situation in which platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) are induced and regulate these VSMC activities. Troglitazone inhibited both bFGF-induced VSMC growth and PDGF-induced VSMC migration as well as VSMC intimal hyperplasia after endothelial injury in rats. 6 In animal models of restenosis after balloon angioplasty, endogen...

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Troglitazone increases the resistance of low density lipoprotein to oxidation in healthy volunteers

Cited by 43 publications

References 40 publications

Pioglitazone Reduces Neointima Volume After Coronary Stent Implantation

Pioglitazone Reduces Neointima Volume After Coronary Stent Implantation

Rapid Effects of Rosiglitazone Treatment on Endothelial Function and Inflammatory Biomarkers

Troglitazone Upregulates Nitric Oxide Synthesis in Vascular Smooth Muscle Cells

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