TNF-alpha induces endothelial dysfunction in diabetic adults, an effect reversible by the PPAR-gamma agonist pioglitazone.
Eur Heart J
; 27(13): 1605-9, 2006 Jul.
Article
em En
| MEDLINE
| ID: mdl-16762982
ABSTRACT
AIMS:
Inflammation contributes to the pathogenesis of cardiovascular disease. Tumour necrosis factor (TNF)-alpha, in particular, is a key mediator of inflammation and vascular dysfunction and progression of atherosclerotic disease. Pioglitazone, a peroxisome proliferator-activated receptor-gamma agonist, not only improves insulin sensitivity, but may also have anti-inflammatory effects. The aims of this study were to investigate the acute effects of local intra-arterial infusion with low-dose TNF-alpha on resistance vessel endothelial function in type 2 diabetes and to determine whether short-term pioglitazone treatment protects against vascular dysfunction induced by this inflammatory stimulus. METHODS ANDRESULTS:
A randomized, parallel, placebo-controlled, double blind trial with 30 mg pioglitazone once daily for 4 weeks was performed in 16 male patients with recently diagnosed type 2 diabetes. Forearm plethysmography (FBF) was used to evaluate the effect on resistance vessel responses of intra-arterial administration of serotonin (NO-dependent vasodilation) and nitroprusside (endothelium-independent vasodilation) followed by another FBF-measurement during the second hour of intra-arterial infusion with TNF-alpha (10 ng/100 mL forearm volume/min for 2 h). Endothelial-dependent FBF of type 2 diabetic patients was significantly impaired (25.4%) by intra-arterial TNF-alpha infusion (P = 0.01), whereas nitroprusside-induced vasodilation did not change. Treatment with pioglitazone for 4 weeks completely blocked TNF-alpha-induced impairment of endothelial-dependent FBF compared with placebo. No significant changes in plasma concentrations of TNF-alpha, interleukin-6, soluble TNF-alpha-receptors, or CD40L were observed.CONCLUSION:
Pioglitazone treatment can convey direct protection against cytokine (TNF-alpha)-induced endothelial dysfunction in humans with an increased cardiovascular risk due to type 2 diabetes.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Endotélio Vascular
/
Fator de Necrose Tumoral alfa
/
Tiazolidinedionas
/
Diabetes Mellitus Tipo 2
/
Angiopatias Diabéticas
/
Hipoglicemiantes
Tipo de estudo:
Clinical_trials
/
Observational_studies
/
Risk_factors_studies
Limite:
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Eur Heart J
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Holanda