Fatty acid oxidation in female cardioprotection

摘要 绝经前女性心血管疾病的发病率明显低于同龄女性 男人。然而，女性心血管疾病的发病率在发病后显著增加。 更年期，导致相对丧失对心脏病的保护。雌激素水平的降低是 与绝经后心脏保护的丧失密切相关，但其背后的生物学机制 它们之间的联系是不完全理解的。虽然我们知道雌激素信号介导了对 不同的病理生理刺激，我们还不完全了解雌激素如何调节关键的代谢途径 在那颗衰竭的心里。在目前的提案中，我们试图了解心脏脂肪的相对减少 酸氧化是绝经后女性心脏失去心脏保护的主要原因。在具体目标1中，我们 将决定雌激素如何控制GCN5L1的丰度，GCN5L1是一种调节心脏脂肪酸的酶 氧化。在特定的目标2中，我们将确定GCN5L1如何调节小鼠的心脏脂肪酸氧化 更年期女性的模特。在具体目标3中，我们将确定对脂肪酸氧化的需求 女性心脏保护。

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.