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CARDIOLOGY: Cell death by necrosis leads to heart failure
The prevalence of heart failure continues to increase in the Western world, making it one of the biggest killers in this region. It is characterized by loss of the muscle cells of the heart (cardiomyocytes). Although this loss is generally considered to occur mostly through a process known as apoptotic cell death, a new study appearing online on August 9, in advance of publication in the September print issue of the Journal of Clinical Investigation, indicates that cell death by necrosis also has a role in the cardiomyocyte loss that accompanies heart failure in mice.
In the study, Jeffery Molkentin and colleagues from Cincinnati Childrens Hospital Medical Center, show that in mice increased Ca2+ influx in cardiomyocytes causes the cells to die by necrosis and the mice to die of heart failure. Necrotic cell death and heart failure were enhanced by agonists of beta-adrenergic receptors and abrogated by inhibitors of beta-adrenergic receptors. They were also abrogated in mice lacking cyclophilin D, which is the regulator of the mitochondrial permeability pore. This demonstration that Ca2+- and mitochondrial-dependent necrotic cardiomyocyte death is a cellular event that contributes to heart failure in mice, led the authors to conclude that heart failure is a pleiotropic disease that involves both apoptotic and necrotic cardiomyocyte death.
TITLE: Ca2+- and mitochondrial-dependent cardiomyocyte necrosis as a primary mediator of heart failure
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Journal of Clinical Investigation