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Fatty acid oxidation in female cardioprotection

脂肪酸氧化对女性心脏的保护作用

基本信息

批准号：
10362454
负责人：
Iain Scott
金额：
$ 53.83万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-12-06 至 2025-11-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10362454
关键词：
Acetylation Acetyltransferase Address Age Attenuated Biochemical Biological Cardiac Cardiac health Cardiovascular Diseases Cell Line Cells Data Development Disease Energy Metabolism Enzymes Estrogen Therapy Estrogens Exhibits Female Future Goals Heart Heart Diseases Heart failure Human In Vitro Incidence Injury Knock-out Knockout Mice Laboratories Link Lysine Measures Mediating Menopause Metabolic Pathway Metabolism Mission Mitochondria Mitochondrial Proteins Modeling Molecular Molecular Target Mus Myocardial dysfunction Myocardium National Heart, Lung, and Blood Institute Output Ovarian Ablation Ovarian Follicle Pathologic Pathway interactions Postmenopause Premenopause Production Protein Acetylation Proteins Regulation Regulator Genes Role Series Signal Transduction Stimulus Stress Testing Therapeutic Intervention Transgenic Mice Wild Type Mouse Woman cardioprotection enzyme activity fatty acid oxidation functional decline heart metabolism improved in vivo male men mouse model novel overexpression pressure response tool young adult

项目摘要

ABSTRACT Pre-menopausal women display a significantly lower incidence of cardiovascular disease than age-matched men. However, the incidence of female cardiovascular disease increases markedly after the onset of menopause, resulting in a relative loss of protection from heart disease. Decreased levels of estrogen are closely linked to the loss of cardioprotection after menopause, but the biological mechanisms underlying this connection are incompletely understood. While we know that estrogen signaling mediates the response to various pathophysiological stimuli, we do not fully understand how estrogen regulates key metabolic pathways in the failing heart. In the current proposal, we seek to understand whether relative reductions in cardiac fatty acid oxidation underpin the loss of cardioprotection in post-menopausal female hearts. In Specific Aim 1, we will determine how estrogen controls the abundance of GCN5L1, an enzyme that regulates cardiac fatty acid oxidation. In Specific Aim 2, we will determine how GCN5L1 regulates cardiac fatty acid oxidation in mouse models of female menopause. In Specific Aim 3, we will determine the requirement for fatty acid oxidation in female cardioprotection.

摘要绝经前妇女的心血管疾病发病率显著低于年龄匹配的男人然而，女性心血管疾病的发病率在发病后明显增加，更年期，导致相对丧失对心脏病的保护。雌激素水平降低与绝经后心脏保护功能的丧失密切相关，但其生物学机制连接不完全理解。虽然我们知道雌激素信号介导了对各种病理生理刺激，我们不完全了解雌激素如何调节关键代谢途径在衰竭的心脏中。在目前的建议中，我们试图了解心脏脂肪酸的相对减少是否酸氧化支持绝经后女性心脏的心脏保护作用的丧失。在具体目标1中，将确定雌激素如何控制GCN 5L1（一种调节心脏脂肪酸的酶）的丰度氧化在具体目标2中，我们将确定GCN 5L1如何调节小鼠心脏脂肪酸氧化女性更年期的模型。在具体目标3中，我们将确定以下条件中对脂肪酸氧化的要求：女性心脏保护