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Apoptose—was ist das?

What is apoptosis? Relevance in coronary heart disease and infarction?

Bedeutung bei koronarer Herzkrankheit und Infarkt

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Zusammenfassung

Apoptose ist ein physiologisches, phylogenetisch hochkonserviertes Programm des regulierten Zellselbstmordes, charakterisiert durch Kernschrumpfung mit DNS-Fragmentierung, durch Phospholipidveränderungen in der Zellmembran und durch Zellschrumpfung. Von Zellmembran umgebene apoptotische Zellreste werden weitgehend ohne Entzündungsreaktion phagozytiert. Die Apoptose wird durch eine Kaskade hochspezifischer Caspasen bewerkstelligt, deren Aktivierung durch Komplexierung von Initiatorcaspasen in Signalkomplexen an den Rezeptoren der TNF-Familie und/oder an geschädigten Mitochondrien erfolgt. Bei vielen Formen des Zellstresses mit Schädigung der Kern-DNS und der Mitochondrien werden Mischformen des Zelluntergangs ausgelöst mit Aktivierung des regulierten Apoptoseprogramms, aber auch mit Elementen der unregulierten, katastrophenartigen Nekrose. Eine derartige Mischform des Myozytenuntergangs besteht auch bei Ischämie und Reperfusion des Myokards. In Experimenten können antiapoptotische Interventionen ischämische Myokardschäden zumindest verzögern, so daß derartige Interventionen als Strategie zur Erweiterung des zeitlichen Spielraums für die Reperfusion denkbar erscheinen. Zur Dauerprävention von myokardialen Ischämieschäden erscheint aber chronische Apoptosehemmung nicht als plausible Strategie wegen der dadurch gestörten Funktion des Immunsystems, wegen mutmaßlich ungünstiger Wirkungen auf arteriosklerotische Läsionen und wegen denkbarer Störungen bei der physiologischen Elimination beschädigter Mitochondrien.

Abstract

Apoptosis is a physiological, highly conserved program of cellular suicide, characterized by nuclear condensation with DNA-fragmentation, by alterations in the distribution of cell membrane phospholipids, and by cellular shrinkage. Apoptotic cellular remnants engulfed by cell membranes are phagocytized largely without activation of inflammatory reactions. The apoptotic program is executed by a cascade of highly specific caspases, activated by complexation of initiatorcaspases in cytosolic signalling complexes at receptors of the TNF family or at impaired mitochondria. In many forms of cellular stress with damage of nuclear DNA and mitochondria, mixed forms of cell death are triggered with regulated activation of the apoptotic program and, concomitantly, with induction of catastrophic necrosis. Such a mixed form of myocyte death is observed in myocardial ischemia and reperfusion. Antiapoptotic interventions can delay ischemic myocardial damage in experiments. Therefore, those interventions appear conceivable as future strategy for acutely enhancing the available time interval for therapeutic reperfusion. However, chronic inhibition of apoptosis for ongoing prevention of myocardial ischemic damage may not become a plausible strategy because of disturbances of the immune system, because of putatively infavorable effects on arteriosclerotic lesions and because of likely disturbances in the physiologic elimination of damaged mitochondria.

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  1. Institut für Pathophysiologie, Martin-Luther-Universität Halle-Wittenberg, Magdeburger Straße 18, D-06097, Halle/Saale

    Jürgen Holtz & Holger Heinrich

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H. Heinrich ist Stipendiat der Deutschen Herzstiftung

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Holtz, J., Heinrich, H. Apoptose—was ist das?. Herz 24, 196–210 (1999). https://doi.org/10.1007/BF03044962

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