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

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Myocardial infarction is associated with increased TUNEL-positivity in cardiac resident and infiltrated cells. Apoptosis of proliferated interstitial myofibroblasts and infiltrated inflammatory cells may have a role in terminating tissue repair processes after infarction. Lateral and endocardial border zones of infarction within the risk area have frequent appearance of TUNEL-positive cardiomyocytes. Although the typical ultrastructural morphology of apoptosis has rarely been detected in ischaemic cardiomyocytes, there are many reports in which the TUNEL method was used for assessment of cardiomyocyte apoptosis. It has become evident that TUNEL- positivity reflects a wide range of cellular conditions; viable cells undergoing DNA repair, apoptosis, and necrosis. Therefore, it is controversial whether TUNEL-positive cardiomyocytes in infarcted myocardium are all apoptotic. Methods which will be more specific for identifying apoptosis are required for future study. TUNEL-positivity can be attenuated by anti-apoptotic interventions such as inhibition of caspases, mitochondrial protection, free radical scavenging, and some conventional pharmacotherapies. However, it remains to be determined whether anti-apoptotic interventions result in satisfactory reduction of infarct size. The injurious impact of myocardial ischaemia comes from a mixture of pro-apoptotic and necrosis- promoting signals, and the target of both signals is mitochondria. Through a common pathway they may cause permeability transition. Interventions which act only at the post-mitochondrial stage of apoptosis may fail to reduce infarct size, whereas those acting at pre-mitochondrial and mitochondrial stages may reduce infarct size. Progress in investigating the basic mechanisms of apoptosis and recognition of the modes of cardiomyocyte death will contribute to advances in cardioprotective therapy in myocardial infarction.

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Yaoita, H., Ogawa, K., Maehara, K., & Maruyama, Y. (2000, February). Apoptosis in relevant clinical situations: Contribution of apoptosis in myocardial infarction. Cardiovascular Research. https://doi.org/10.1016/S0008-6363(99)00349-1

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