Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA.
IUBMB Life. 2013 Aug;65(8):651-6. doi: 10.1002/iub.1180. Epub 2013 Jul 3.
Loss of cardiomyocytes plays a critical role in the pathogenesis of heart failure. With fewer myocytes, the heart is unable to sustain efficient contraction. Much attention has been focused on understanding mechanisms of cell death in myocytes with the ultimate goal being to reduce the extent of injury and improve function in the failing myocardium. Both necrosis and apoptosis contribute to loss of myocytes, and this loss of cells is a hallmark of cardiac pathologies, including ischemia/reperfusion, myocardial infarction, and heart failure. Apoptosis is a highly regulated process that is activated via death receptors in the plasma membrane or via permeabilization of the mitochondria. Necrosis is generally viewed as an uncontrolled process that leads to mitochondrial swelling, cell rupture, and subsequent inflammation. However, recent studies have uncovered a signaling pathway that mediates regulated necrosis or necroptosis. Mitochondria play an important role in both apoptosis and necrosis, and changes in their morphology can affect the cells' susceptibility to stress. This review focuses on the various modes of cell death in the myocardium and highlights how they contribute to loss of myocytes in response to stress.
心肌细胞的损失在心力衰竭的发病机制中起着关键作用。心肌细胞减少，心脏就无法维持有效的收缩。人们非常关注理解心肌细胞死亡的机制，最终目标是减少损伤程度，改善衰竭心肌的功能。坏死和凋亡都导致心肌细胞的损失，而这种细胞损失是包括缺血/再灌注、心肌梗死和心力衰竭在内的心脏病理的一个标志。凋亡是一种高度受调控的过程，通过质膜上的死亡受体或通过线粒体通透性的增加而被激活。坏死通常被认为是一种失控的过程，导致线粒体肿胀、细胞破裂和随后的炎症。然而，最近的研究揭示了一种介导调节性坏死或坏死性凋亡的信号通路。线粒体在凋亡和坏死中都起着重要作用，其形态的变化会影响细胞对压力的敏感性。这篇综述重点介绍了心肌细胞的各种死亡方式，并强调了它们如何导致心肌细胞在应激反应中丢失。
