Apoptosis of Cardiomyosites in Heart Disease

Abstract

Although the notion that apoptosis can act as a pathogenic mediator came somewhat later to car-diovascular medicine than to other fields of medicine, research into the role of apoptosis in heart disease has progressed explosively during the past 10 years. Consequently, we now have much information about apoptosis in cardiac cells, collected in vitro and in vivo under a wide variety of pathological conditions using both experimental animal models and specimens from heart disease patients, and there are a number of excellent reviews dealing with the role of apopto-sis in heart disease [1–11].

Among the various cardiovascular ailments, myocardial infarction (MI) is particularly note-worthy for having high rates of both mortality and morbidity. Patients experiencing MI are at risk of sudden death during the acute stage and then ven-tricular remodeling and heart failure during the chronic stage, with the most critical determinant of the remodeling being the magnitude of the acute infarct (i.e., the number of dead cardiomy-ocytes resulting from the acute ischemic insult). In addition, other factors, including late death or hypertrophy of cardiomyocytes, fibrosis and the expression of various cytokines, are associated with the continued disease progression during the chronic stage. Notably, apoptosis has been detect-ed in the heart during all stages of MI, suggesting apoptosis may be responsible for a significant amount of cardiomyocyte death during the acute ischemic stage, as well as for a progressive loss of surviving cells during the subacute and chronic stages. Patients who survive large MIs are at espe-cially high risk of developing such failure. Indeed, patients with post-infarct heart failure account for 44% of candidates for cardiac trans-plantation [12].

Heart failure is the final outcome of a number of heart diseases. Although the mechanisms for cardiac decompensation have not been fully elu-cidated, loss of cardiac myocytes has been con-sidered important as well as dysfunction of indi-vidual cardiac myocytes for one of the mecha-nisms. Extensive study now indicates that apopto-sis is deeply involved in the pathology of almost all types of heart disease, not only ischemia-relat-ed ailments (ischemia-reperfusion, the acute and chronic stages of MI, ischemic cardiomyopathy and hibernating myocardium), but also other heart diseases such as dilated cardiomyopathy. Thus, apoptosis appears to be established as one impor-tant mode of cardiomyocyte death that is respon-sible for the development and worsening of heart failure. Other than ischemic hearts and failing hearts, cardiac arrhythmias is an important dis-ease entity where apoptosis is suggested to play a role in the pathogenesis [13–16].