Apoptotic cell death in heart failure
Authors: H Sabbah
Journal: Cardiovascular Research (2000)

Introductionwas only recently put forward [11].Studies in dogs with heart failure produced by intracoronary microemboliza-Progressive deterioration of left ventricular (LV) func-tions showed, for the first time, that progressive LV tion is a characteristic feature of the failing heart.This dysfunction was associated with increased volume fraction hemodynamic deterioration, often accompanied by worsen-of replacement fibrosis [11] or, in other words, increased ing of clinical symptoms, occurs despite the absence of proportion of scarred to viable myocardium suggesting clinically apparent intercurrent adverse events [1,2] and, ongoing myocyte loss.While these studies provided supinvariably, culminates in the syndrome of congestive heart port to the concept of ongoing loss of viable myocardium failure.The exact mechanisms that drive this process are in the failing heart, the means by which myocytes were not known.For years, a so-called 'vicious circle' postulate lost was not identified.Even before these studies where was adopted to explain this phenomenon whereby compen-completed, investigations in dogs with heart failure [12] satory mechanisms, elicited to maintain homeostasis, them-and in explanted failed human hearts [13,14] showed that selves become factors that exacerbate the heart failure cardiomyocyte death through apoptosis occurs in advanced state.Such compensatory mechanisms included LV hy-heart failure, a finding that supports the original working pertrophy, LV chamber dilation, and enhanced and sus-hypothesis.In this review, results of research in extained activity of the sympathetic nervous system and perimental animals as well as in humans on the identificarenin-angiotensin system [3][4][5][6].In recent years, we and tion of cardiomyocyte apoptosis in heart failure will be others have put forward a working hypothesis that progres-discussed.The discussion will also address potential sive LV dysfunction in heart failure may result, in part, molecular and pathophysiological triggers that may drive from ongoing loss of cardiomyocytes.The notion that this process of cell death in the failing heart.Finally, an progression of heart failure may be due, in part, to ongoing attempt will be made to address a central theme of whether loss of functional cardiac units was based on the presence cardiomyocyte apoptosis plays an important role in the of ultrastructural degenerative changes of cardiomyocytes progression of LV dysfunction that is characteristic of the in the failed human heart as well as in hearts of animals heart failure state.with experimentally-induced heart failure [7-10].Structur-Unlike necrosis, apoptosis is an active, precisely regal abnormalities included myofibrillar disruption and dis-ulated, energy requiring process which appears to be array [8], abnormalities of mitochondria characterized by orchestrated by a genetic program [15] and hence the disruption of the internal and external membranes, hy-interchangeable use of the terms 'apoptosis' and 'properplasia and reduced organelle size [7], and abnormalities grammed cell death'.Apoptosis plays a crucial role in the of the cardiac interstitium characterized by accumulation regulation of proliferating cell populations in adult tissues of collagen [9].These observations provided some support, and in normal tissue development [16,17].Cells such as albeit indirect, to the concept that ongoing myocyte neurons and cardiac myocytes, even though terminally degeneration and loss may occur in the failing heart.differentiated contain the genes and signal transduction Objective evidence in support of this concept, however, pathways necessary for programmed cell death and thus retain the ability to die by apoptosis [18].In humans and