Apoptosis in relevant clinical situations: contribution of apoptosis in myocardial infarction

Myocardial infarction is associated with increased TUNEL-positivity in card iac resident and infiltrated cells. Apoptosis of proliferated interstitial myofibroblasts and infiltrated inflammatory cells may have a role in termin ating tissue repair processes after infarction. Lateral and endocardial bor der zones of infarction within the risk area have frequent appearance of TU NEL-positive cardiomyocytes. Although the typical ultrastructural morpholog y of apoptosis has rarely been detected in ischaemic cardiomyocytes, there are many reports in which the TUNEL method was used for assessment of cardi omyocyte apoptosis. It has become evident that TUNEL-positivity reflects a wide range of cellular conditions; viable cells undergoing DNA repair, apop tosis, and necrosis. Therefore, it is controversial whether TUNEL-positive cardiomyocytes in infarcted myocardium are all apoptotic. Methods which wil l be more specific for identifying apoptosis;,ii are required for future st udy. TUNEL-positivity can be attenuated by anti-apoptotic interventions suc h as inhibition of caspases, mitochondrial protection, free radical scaveng ing, and some conventional pharmacotherapies. However, it remains to be det ermined :II( whether anti-apoptotic interventions result in satisfactory re duction of infarct size. The injurious impact of myocardial ischaemia comes from a mixture of pro-apoptotic and necrosis-promoting signals, and the ta rget of both signals is mitochondria. Through a common pathway they may cau se permeability transition, interventions which act only at the post-mitoch ondrial stage of apoptosis may fair to : II reduce infarct size, whereas th ose acting at pre-mitochondrial and mitochondrial stages may reduce infarct size. Progress in investigating the basic mechanisms of apoptosis and reco gnition of the modes of cardiomyocyte death will contribute to advances in cardioprotective therapy in myocardial infarction. (C) 2000 Elsevier Scienc e B.V. All rights reserved.