Transgenic MMP-2 expression induces latent cardiac mitochondrial dysfunction.
Biochem Biophys Res Commun
; 358(1): 189-95, 2007 Jun 22.
Article
em En
| MEDLINE
| ID: mdl-17475219
ABSTRACT
Matrix metalloproteinases (MMPs) are central to the development and progression of dysfunctional ventricular remodeling after tissue injury. We studied 6 month old heterozygous mice with cardiac-specific transgenic expression of active MMP-2 (MMP-2 Tg). MMP-2 Tg hearts showed no substantial gross alteration of cardiac phenotype compared to age-matched wild-type littermates. However, buffer perfused MMP-2 Tg hearts subjected to 30 min of global ischemia followed by 30 min of reperfusion had a larger infarct size and greater depression in contractile performance compared to wild-type hearts. Importantly, cardioprotection mediated by ischemic preconditioning (IPC) was completely abolished in MMP-2 Tg hearts, as shown by abnormalities in mitochondrial ultrastructure and impaired respiration, increased lipid peroxidation, cell necrosis and persistently reduced recovery of contractile performance during post-ischemic reperfusion. We conclude that MMP-2 functions not only as a proteolytic enzyme but also as a previously unrecognized active negative regulator of mitochondrial function during superimposed oxidative stress.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Metaloproteinase 2 da Matriz
/
Mitocôndrias Cardíacas
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Miocárdio
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article