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Mechanisms involved in male-female differences in cardioprotection

男女心脏保护差异的机制

基本信息

批准号：
10929085
负责人：
Elizabeth Murphy
金额：
$ 42.33万
依托单位：
NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10929085
关键词：
Acute Animal Model Animals Binding Calcium Cardiovascular Diseases Cardiovascular system Cell membrane Clinical Trials Data Estrogen Nuclear Receptor Estrogens Female Genes Goals Heart Heart Diseases Heat shock proteins Hormone replacement therapy Hypertrophy Incidence Infarction Injury Ischemia Location Measures Methods Mitochondria Modeling Nitric Oxide Nitric Oxide Synthase Outcome PIK3CG gene Pathway interactions Perfusion Post-Translational Protein Processing Postmenopause Premenopause Proteins Reperfusion Injury Reperfusion Therapy Reporting Role Selective Estrogen Receptor Modulators Sex Differences Signal Transduction Sodium-Calcium Exchanger Testing Woman Women&apos s Health beta-adrenergic receptor cardioprotection cardiovascular disorder risk gender disparity ischemic injury male non-genomic overexpression phospholamban response uptake

项目摘要

Although gender disparities in cardiac disease are recognized, the mechanisms through which pre-menopausal females are protected have not been fully elucidated. Cardiac disease incidence in females increases post-menopause, suggesting a role for estrogen in pre-menopausal cardioprotection. However, clinical trials found no beneficial cardiovascular outcomes from hormone replacement therapy, indicating a better mechanistic understanding is needed. Thus the goal of this study is to understand the mechanism responsible for the male-female differences in ischemia-reperfusion injury, cardioprotection and hypertrophy. We reported previously that under conditions of calcium overload, as occurs with overexpression of plasma membrane sodium-calcium exchanger, loss of phospholamban or overexpression of beta-adrenergic receptor, females have less I/R injury. We developed methods to measure mitochondrial calcium during I/R to test whether there are sex differences in mitochondrial calcium uptake during I/R. With our new method to measure mitochondrial calcium during I/R we are tested whether there are sex differences in mitochondrial calcium uptake during I/R. Our preliminary studies show that during ischemia female accumulate less mitochondrial calcium than males. We are testing to see whether these differences are due to alterations in mitochondrial calcium uptake or efflux mechanisms.

虽然心脏病的性别差异是公认的，但绝经前女性受到保护的机制尚未完全阐明。绝经后女性心脏病发病率增加，提示雌激素在绝经前心脏保护中的作用。然而，临床试验没有发现激素替代疗法对心血管有益的结果，这表明需要更好的机制理解。因此，本研究的目的是了解男女在缺血再灌注损伤、心脏保护和肥厚方面差异的机制。