title: Ultrastructural definition of apoptosis in heart failure.
abstract: Cardiac myocytes die through apoptosis, oncosis, and autophagy. Apoptosis affects single cells and is morphologically characterized by nuclear fragmentation with generation of apoptotic bodies that can be seen either within dying cells or free in the interstitial spaces. Dead myocytes are removed by macrophages through phagocytosis without triggering inflammation. The circulating markers of myocyte necrosis are not increased by apoptosis. The morphologic changes of the induction and early execution phases are seen at electron microscopy while late fragmentation is visible on both light and electron microscopy. Immunoelectron microscopy provides combined functional and structural information showing cytochrome c immuno-labelling release from mitochondria, TUNEL labelling of apoptotic nuclei, annexin V translocation in the outer plasma cell layer. Oncosis is characterized by specific morphologic features that may coexist with apoptosis, especially in ischemic myocardium. Autophagy is a defense process that is associated with significant myocardial damage and necrosis when removal of the lysosomal content is impaired. Morphological features of apoptosis, oncosis, and autophagocytosis may coexist at the same time. Although dead myocytes showing characteristics of autophagy and apoptosis are rarely observed in human decompensated hearts, autophagic vacuoles, and early apoptotic changes may be seen more often in morphologically viable myocytes. Such features may occur in failing hearts of both ischemic and non-ischemic etiology. The shared mode of cardiac myocyte death in failing human hearts of different etiologies suggests that preservation of myocyte integrity may be possible by similar therapeutic strategies.
authors.affiliation: Centro Malattie Genetiche Cardiovascolari, Fondazione IRCCS, Policlinico San Matteo, Pavia, Italy. e.arbustini@smatteo.pv.it
authors.forename: Eloisa
authors.initials: E
authors.lastname: Arbustini
authors.forename: Agnese
authors.initials: A
authors.lastname: Brega
authors.forename: Jagat
authors.initials: J
authors.lastname: Narula
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D006333:Heart Failure / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008854:Microscopy, Electron; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000648:ultrastructure*