Role of mitochondria in cardiac ischemia

总结 心力衰竭是世界范围内死亡的主要原因。心肌梗死有 已被证明是心力衰竭的最常见原因。有效治疗 需要开发用于预防和治疗心肌梗塞的策略。 细胞凋亡是心肌梗死的一种死亡形式。为了保持心脏 在结构和功能上都是完整的，有必要防止细胞凋亡， 不会丢失心肌细胞。众所周知，心肌细胞富含 线粒体线粒体一方面为心脏功能提供能量， 另一方面参与细胞凋亡的启动。最近的研究表明， 揭示了线粒体异常分裂在调节 凋亡然而，线粒体分裂在心脏疾病中的作用一直是 研究较少。此外，线粒体分裂的分子调控， 心肌细胞仍然是未知的。我们的长期目标是研究 线粒体在心脏病理生理学中的作用Prohibitin是一种心脏丰富的蛋白质。的 抑制素在心脏中的功能尚未阐明。miRNAs参与了 调节心脏生理和病理，但目前尚不清楚是否miRNAs是 能够调节线粒体分裂机制。我们已经清楚地观察到 显示抑制素和miRNA水平响应于氧化应激而改变， 心肌缺血此外，抑制素可以防止线粒体分裂， 心肌细胞凋亡。我们假设miRNA和prohibitin构成了一个 在调节心脏线粒体分裂和凋亡中起重要作用。研究报告 aim-1和aim-2将表征prohibitin是否可以被miRNA靶向，并且 它们在线粒体分裂和凋亡中的作用。目标3下的研究将探讨 抑制素调节线粒体分裂和凋亡的分子机制。 AIM-4研究将测试抑制素是否能影响心肌梗死 由缺血/再灌注诱导。这个项目不仅有助于理解 线粒体分裂及其在心脏中的分子调节，也可导致进一步的 研究开发介入治疗的创新方法， 心肌梗塞等心脏病。

Summary Heart failure is a leading cause of mortality worldwide. Myocardial infarction has been proved to be the most common cause of heart failure. The effective therapeutic strategies need to be developed for the prevention and treatment of myocardial infarction. Apoptosis is a type of death form in myocardial infarction. In order to maintain the heart intact in both structure and function, it is necessary to prevent apoptosis so that the heart does not lose cardiomyocytes. It is well known that cardiomyocytes are enriched in mitochondria. Mitochondria on one hand supply energy for the heart function, they on the other hand participate in the initiation of apoptosis. The most recent studies have revealed that mitochondrial abnormal fission plays a critical role in the regulation of apoptosis. However, the role of mitochondrial fission in the cardiac diseases has been less studied. Furthermore, the molecular regulation of mitochondrial fission in cardiomyocytes remains largely unknown. Our long term goal is to study the role of mitochondria in cardiac pathophysiology. Prohibitin is a cardiac abundant protein. The function of prohibitin in the heart has not yet been clarified. miRNAs are involved in the regulation of cardiac physiology and pathology, but it is unknown whether miRNAs are able to regulate mitochondrial fission machinery. We have made observations clearly showing that prohibitin and miRNA levels are altered in response to oxidative stress and cardiac ischemia. Furthermore, prohibitin can prevent mitochondrial fission and apoptosis in cardiomyocytes. We hypothesize that miRNA and prohibitin constitute an axis in the regulation of mitochondrial fission and apoptosis in the heart. Studies under aim-1 and aim-2 will characterize whether prohibitin can be targeted by the miRNA, and their roles in mitochondrial fission and apoptosis. Studies under aim-3 will explore the molecular mechanism by which prohibitin regulate mitochondrial fission and apoptosis. Studies under aim-4 will test whether prohibitin can influence myocardial infarction induced by ischemia/reperfusion. This proposed project will not only help understand mitochondrial fission and its molecular regulation in the heart, but also can lead to further studies to develop the innovative approaches for the interventional treatment of apoptosis-related cardiac diseases such as myocardial infarction.