Apoptosis in Heart Failure

pp 603-607

Abstract

Progressive myocardial disfunction in heart failure (HF) is due -at least partially- to the loss of cardiac myocytes because of apoptosis or programmed cell death according to a genetic program, with energy expenditure. Structural abnormalities distinctive of apoptosis include myofibrillar disruption, mitochondrial abnormalities -seen as internal and external membrane disruption- hyperplasic and decrement in organelle size, collagen deposition in cardyac interstitium, blebbing of plasma membrane, cell shrinkage and chromatine condensation and fragmentation. Cells fragment in many apoptotic bodies, without loosing plasma membrane integrity. Fragments are phagocitized by macrophages or related cells non-differentiated as macrophages. Apoptosis occurs ina short time lapse (hours), making it difficult its identification and quantification. A key phenomenom of the apoptoptic process is the activation of a unique class of cysteine proteases, specially named as "caspases". At present 14 homologues have been identified in this class. Caspases can propagate the apoptotic signal by unfolding or activation of other enzymes in the group, or can perform terminal events in the apoptotic process, unfolding critical substrates to allow cellular death. There is a body of evidence suggesting that apoptosis can be induced by the same agents responsible of necrosis, according to the kind of cell death, depending on the severity of the pathological stimulus. Such stimuli are: increased levels of catecholamines, angiotensin II, inflammatory cytokines, superoxide anion, reperfusion damage, growth factors, mechanical stretching of myofibers, increases in cytosolic calcium levels and hypoxia. Evidence of myocyte apoptosis in patients with advanced HF, may be one of the factors responsible of progression of myocardiopathies to severe forms of HF. Future research should provide a deeper knowledge of pathological and molecular criteria to verify the development and extension of apoptosis in cardiac myocytes with additional sensitivity and specificity.