Abstract

BackgroundAcute myocardial infarction and associated ischemia/reperfusion (I/R) injury remains a leading cause of death in older post‐menopausal women. I/R injury triggers mitochondrial dysfunction leading to necrosis, apoptosis, and/or autophagy.PurposeTo determine if age‐associated estrogen deficiency alters mitochondrial morphology in conjunction with vulnerability to I/R injury.MethodsMitochondrial morphology was assessed through electron microscopy in border zone regions following coronary artery ligation (55 min I and 4–6 hr R) or sham in adult (6 mo) ovary‐intact, aged (24 mo) ovary‐intact and aged ovariectomized (OVX) female F344 rats. Necrosis was assessed by triphenyltetrazolium chloride staining, apoptosis by DNA laddering and TUNEL, and markers of autophagy by western blotting.ResultsLoss of mitochondrial matrix following I/R was greatest in aged OVX. Mitochondrial area was less in aged vs adult in conjunction with increased mitochondrial number and marked Z line streaming. Reduced DNA laddering and TUNEL, combined with increased beclin‐1 and cathepsinD in aged vs adult, further support a dominant role for necrosis underlying cell death in aged females (n=4–5/group).ConclusionMorphological alterations in mitochondria with aging are likely contributory in necrotic cell death mechanisms associated with I/R injury in post‐menopausal women.

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