Cell death signalling mechanisms in heart failure.

Cardiac disease is a global epidemic that is on the rise, despite the recent advances in cardiovascular research. Once the myocardium is injured, it has a limited capacity to activate reparative mechanisms to restore proper cardiac function, leading to the development of systemic heart failure. Autophagy, under certain conditions, may result in cell death, further emphasizing the controversial issues regarding the autophagic process as an adaptive or maladaptive biological response. Although significant progress in understanding the signalling mechanisms of cell death in myocytes has been made, the role of apoptotic cell death and programmed necrosis during heart failure is not completely understood. Insight to how myocytes determine whether to activate apoptotic or programmed necrosis signalling machinery remains under current investigation because it is a major problem for both scientists and clinicians in treating heart failure patients. Herein, the different modes of cell death implicated in heart failure are highlighted, as well as the role of B-cell lymphoma-2 family members and how mitochondria act as central organelles in directing such cell death mechanisms.