Apoptosis in heart failure.
A characteristic feature of heart failure is the progressive worsening of ventricular function over months or years despite the absence of clinically apparent intercurrent adverse events. The mechanism or mechanisms responsible for this hemodynamic deterioration are not known but may be related to progressive intrinsic contractile dysfunction of residual viable cardiac myocytes, or to ongoing degeneration and loss of myocytes, or both. This report will address the concept of ongoing cardiac myocyte loss that may occur during the course of evolving heart failure viewed from the perspective of apoptosis or "programmed cell death" as the potential mediator of cardiac muscle cell loss. In recent years, several studies have shown that constituent myocytes of failed explanted human hearts and hearts of animals with experimentally induced heart failure undergo apoptosis. Recent studies have shown that cardiac myocyte apoptosis also occurs after acute myocardial infarction, as well as in the hypertrophied heart and the aging heart, conditions frequently associated with the development of heart failure. Considerable work has also been conducted and novel concepts advanced to explain potential molecular triggers of cardiac myocyte apoptosis in heart failure. Although available data support the existence of myocyte apoptosis in the failing heart, questions essential to our understanding of the importance of myocyte apoptosis in this disease process remain unanswered. Lacking are studies aimed at identifying physiological factors inherent to heart failure that trigger myocyte apoptosis. Also lacking are studies that address the importance of myocyte apoptosis in the progression of left ventricular dysfunction. If loss of cardiac myocytes through apoptosis can be shown to be an important contributor to the progression of heart failure, and if factors that trigger apoptosis in the heart can be identified, such knowledge can potentially lead to the development of novel therapeutic modalities aimed at preventing, or at the very least retarding, the process of progressive ventricular dysfunction and the ultimate transition toward end-stage, intractable heart failure.
Sabbah
H N
HN
Department of Medicine, Henry Ford Heart and Vascular Institute, Detroit, MI, USA.
Sharov
V G
VG
D000818:Animals; D017209:Apoptosis; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology; D009203:Myocardial Infarction / Q000503:physiopathology; D009336:Necrosis; D015427:Reperfusion Injury / Q000503:physiopathology