Cell Death By Necrosis Leads To Heart Failure

In the study, Jeffery Molkentin and colleagues from Cincinnati Children's 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.

The study "Ca2+- and mitochondrial-dependent cardiomyocyte necrosis as a primary mediator of heart failure" was published online on August 9, in advance of publication in the September print issue of the Journal of Clinical Investigation.