Abstract 3033: Are There Gender Differences in Cardioprotection? Influence of Aging and Endothelial Nitric Oxide Synthase (eNOS)
Gender differences in incidence and outcome of myocardial infarction (MI) have been reported but the underlying mechanisms remain unclear. The risk and prevalence of acute MI increase progressively with age and levels in females approach those in males after the fifth decade of life. Interestingly, estrogen-induced increase in the eNOS-NO signaling pathway has been reported to play an important role in cardioprotection in females. While ischemic preconditioning (IPC) provides robust endogenous cardioprotection with reduced myocardial infarction, there is no consensus as to whether the effects of IPC are maintained in the aging heart, and if there are differences with gender or in the role of eNOS-NO signaling in conferring protection. Therefore, we performed IPC in wild-type (WT) and eNOS-knockout (eNOS-KO) mice to evaluate whether the infarct limiting effect of IPC depends on gender, age (8 –12 weeks vs. 12–18 months), and eNOS. Classical IPC was induced by 3-cycles of 5-min regional coronary ischemia separated by 5-min reperfusion, and was followed by 30-min index ischemia and 24-hr reperfusion. Control ischemia/reperfusion (I/R) had 30-min I followed by 24-hr R. Protection was evaluated by measuring infarct size as % area at risk (Table⇓). We observe that aging increased myocardial infarct size in WT and eNOS-KO mice of both genders following I/R, but female WT mice exhibited significantly smaller infarction compared to male WT mice at both ages. This gender associated protection was lost with eNOS-KO. While, the infarct reducing effect of IPC was well maintained in young and aged female WT mice, it was reduced in aged male WT mice. Importantly, regardless of gender and age, the protective effects of IPC were absent in eNOS-KO mice. Thus, eNOS is required for the gender associated protection against I/R seen in females and is required for the induction of IPC in both male and female mice.