Pioglitazone, a peroxisome proliferator-activated receptor-gamma agonist, attenuates left ventricular remodeling and failure after experimental myocardial infarction.
Circulation
; 106(24): 3126-32, 2002 Dec 10.
Article
em En
| MEDLINE
| ID: mdl-12473562
ABSTRACT
BACKGROUND:
Peroxisome proliferator-activated receptor-gamma activators have recently been implicated as regulators of cellular proliferation and inflammatory response such as cytokine expression. Because proinflammatory cytokines play a critical role in left ventricular (LV) remodeling after myocardial infarction (MI), we examined the effects of pioglitazone treatment in an experimental model of chronic heart failure. METHODS ANDRESULTS:
Mice with extensive anterior MI were treated with placebo or pioglitazone (3 mg x kg(-1) x d(-1)) as a dietary supplement for 4 weeks starting 6 hours after surgery. Infarct size and glucose levels were similar among all groups. LV cavity dilatation and dysfunction by echocardiography were significantly attenuated in MI mice given pioglitazone. LV end-diastolic pressure was increased in MI mice and was significantly reduced by pioglitazone treatment. Pioglitazone partially normalized LV dP/dt(max) and dP/dt(min), indices of LV contractile function, which were significantly reduced in MI mice. Improvement of LV function by pioglitazone was accompanied by a decrease in myocyte hypertrophy and interstitial fibrosis and a reduced expression of tumor necrosis factor-alpha, transforming growth factor-beta, and monocyte chemoattractant protein-1 genes in the noninfarcted LV from MI mice. LV inducible nitric oxide synthase and gelatinase B protein levels were increased in MI and were not altered by pioglitazone treatment.CONCLUSIONS:
Pioglitazone improved LV remodeling and function in mice with post-MI heart failure. This effect was associated with an attenuated LV expression of inflammatory cytokines and chemokines. Peroxisome proliferator-activated receptor-gamma ligands have promise as preventive and therapeutic agents against heart failure.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Tiazóis
/
Fatores de Transcrição
/
Receptores Citoplasmáticos e Nucleares
/
Remodelação Ventricular
/
Tiazolidinedionas
/
Insuficiência Cardíaca
/
Infarto do Miocárdio
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Idioma:
En
Revista:
Circulation
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
Japão