Adiponectin mediates the suppressive effect of rosiglitazone on plasminogen activator inhibitor-1 production.
Arterioscler Thromb Vasc Biol
; 27(12): 2777-82, 2007 Dec.
Article
em En
| MEDLINE
| ID: mdl-17932317
ABSTRACT
OBJECTIVE:
The purpose of this study was to examine the effects of PPAR-gamma agonist rosiglitazone, relative to sulfonylureas, on circulating levels of adiponectin and the prothrombotic factor, plasminogen activator inhibitor (PAI)-1, in type 2 diabetic patients, and to investigate, in animal models, whether the antithrombotic action of rosiglitazone was mediated through adiponectin. METHODS ANDRESULTS:
Our clinical study (n=64) showed that after 24-week add-on therapy, the rosiglitazone group had a greater mean reduction in plasma PAI-1 levels (25%, versus 12% in sulfonylurea group, P=0.002). Stepwise multiple linear regression analysis identified the reduction in plasma fasting glucose and the rise in adiponectin levels to be independently associated with the reduction in PAI-I concentration in the rosiglitazone-treated patients. Rosiglitazone (20 mg/kg/d) reduced adipose tissue PAI-1 mRNA expression and its plasma levels in wild-type C57 mice with diet-induced obesity (P<0.001), but this suppressive effect was attenuated in adiponectin knockout mice. Adenovirus-mediated overexpression of adiponectin led to a significant suppression of adipose tissue PAI-1 expression and its circulating concentrations in db/db diabetic mice. Our in vitro study demonstrated that recombinant adiponectin directly inhibited PAI-1 production in 3T3-L1 adipocytes.CONCLUSIONS:
The antithrombotic effect of rosiglitazone is mediated, at least in part, through the suppressive effect of adiponectin on PAI-1 production.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos de Sulfonilureia
/
Inibidor 1 de Ativador de Plasminogênio
/
Tiazolidinedionas
/
PPAR gama
/
Diabetes Mellitus Tipo 2
/
Adiponectina
/
Fibrinolíticos
/
Hipoglicemiantes
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Idioma:
En
Revista:
Arterioscler Thromb Vasc Biol
Assunto da revista:
ANGIOLOGIA
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
China