Key result
Aging mice exhibited increased mortality and cardiomyocyte apoptosis following myocardial infarction, and were resistant to caspase inhibition compared to young mice (84% reduction in apoptosis, P<0.05).
Why the study?
Does caspase inhibition with Ac-DEVD-CHO reduce cardiomyocyte apoptosis following myocardial infarction in aging mice compared to young mice?
Does caspase inhibition with Ac-DEVD-CHO reduce cardiomyocyte apoptosis following myocardial infarction in aging mice compared to young mice?
Aging mice exhibit distinct apoptotic pathways and resistance to caspase inhibition following myocardial infarction, suggesting novel or combination approaches may be required for older patients.
Caspase inhibition may fail to limit apoptosis in older post-MI patients; leaves open age-specific anti-apoptotic strategies.
BACKGROUND: Aging is associated with higher incidence of heart failure and death following myocardial infarction (MI). The molecular and cellular changes that lead to these worse outcomes are not known. METHODS AND RESULTS: Young and aging mice underwent induction of MI by LAD ligation. There was a significant increase in mortality in the aging mice. Neither the young nor aging hearts after MI had inducible ventricular tachycardia. Cardiomyocyte apoptosis increases early after MI in young and aging mice, but to a much greater degree in the aging mice. Caspase inhibition with Ac-DEVD-CHO resulted in a 61% reduction in activated caspase-3 and an 84% reduction in apoptosis in cardiomyocytes in young mice (P < 0.05), but not in aging mice. Gene pathway profiling demonstrated activation of both the caspase and Map3k1/Mapk10 pathways in aging mice following MI, which may contribute to their resistance to caspase inhibition. CONCLUSIONS: Aging hearts activate distinct apoptotic pathways have more cardiomyocyte apoptosis and are resistant to antiapoptotic therapies following MI. Novel or combination approaches may be required to improve outcomes in aging patients following MI.
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Boyle et al. (2013) studied Myocardial infarction. Aging vs. Young mice was evaluated on Cardiomyocyte apoptosis and mortality. Aging mice exhibited increased mortality and cardiomyocyte apoptosis following myocardial infarction, and were resistant to caspase inhibition compared to young mice (84% reduction in apoptosis, P<0.05).
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