RESUMO
BACKGROUND: Ataxiatelangiectasia results from mutations in ataxia telangiectasia mutated kinase (ATM) gene. We recently reported that ATM deficiency attenuates left ventricular (LV) dysfunction and dilatation 7 days after myocardial infarction (MI) with increased apoptosis and fibrosis. Here we investigated the role of ATM in the induction of inflammatory response, and activation of survival signaling molecules in the heart acute postMI. METHODS AND RESULTS: LV structure, function, inflammatory response, and biochemical parameters were measured in wildtype (WT) and ATM heterozygous knockout (hKO) mice 1 and 3 days postMI. ATM deficiency had no effect on infarct size. MIinduced decline in heart function, as measured by changes in percent fractional shortening, ejection fraction and LV end systolic and diastolic volumes, was lower in hKOMI versus WTMI (n=10 to 12). The number of neutrophils and macrophages was significantly lower in the infarct LV region of hKO versus WT 1 day postMI. Fibrosis and expression of αsmooth muscle actin (myofibroblast marker) were higher in hKOMI, while active TGFß1 levels were higher in the WTMI 3 days postMI. Myocyte crosssectional area was higher in hKOsham with no difference between the two MI groups. MMP9 protein levels were similarly increased in the infarct LV region of both MI groups. Apoptosis was significantly higher in the infarct LV region of hKO at both time points. Akt activation was lower, while Bax expression was higher in hKOMI infarct. CONCLUSION: ATM deficiency results in decreased dilative remodeling and delays inflammatory response acute postMI. However, it associates with increased fibrosis and apoptosis.