Involvement of CD95/Apo1/Fas in cell death after myocardial ischemia

The death of cardiac cells during ischemia and reperfusion is partially mediated by apoptosis, as seen, eg, in autopsy material of patients after acute myocardial infarction. To study the role of CD95/Fas/Apo1 for induction of postischemic cell death, we used an ischemia/reperfusion model of isolate...

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Bibliographic Details
Published in:Circulation (New York, N.Y.) N.Y.), 2000-08, Vol.102 (8), p.915-920
Main Authors: Jeremias, I, Kupatt, C, Martin-Villalba, A, Habazettl, H, Schenkel, J, Boekstegers, P, Debatin, K M
Format: Article
Language:English
Subjects:
Amino Acid Chloromethyl Ketones - pharmacology
Animals
Apoptosis - physiology
Apoptosis Regulatory Proteins
Caspase Inhibitors
Caspases - physiology
Cell Death - physiology
Cells, Cultured
Cysteine Proteinase Inhibitors - pharmacology
Fas Ligand Protein
fas Receptor - physiology
Heart - physiology
In Vitro Techniques
Male
Membrane Glycoproteins - biosynthesis
Membrane Glycoproteins - metabolism
Mice
Mice, Inbred C57BL
Myocardial Ischemia - metabolism
Myocardial Ischemia - pathology
Myocardial Reperfusion Injury - metabolism
Myocardial Reperfusion Injury - pathology
Myocardium - cytology
Myocardium - metabolism
Myocardium - pathology
Rats
Rats, Wistar
Solubility
TNF-Related Apoptosis-Inducing Ligand
Tumor Necrosis Factor-alpha - biosynthesis
Tumor Necrosis Factor-alpha - metabolism
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Summary:The death of cardiac cells during ischemia and reperfusion is partially mediated by apoptosis, as seen, eg, in autopsy material of patients after acute myocardial infarction. To study the role of CD95/Fas/Apo1 for induction of postischemic cell death, we used an ischemia/reperfusion model of isolated rat and mouse hearts in Langendorff perfusion. In this model, caspase-dependent apoptosis occurred during postischemic reperfusion. Moreover, soluble CD95 ligand/Fas ligand was released by the postischemic hearts early after the onset of reperfusion. In addition, this ligand was synthesized de novo under these circumstances. Similar findings were observed for other "death-inducing" ligands, such as tumor necrosis factor (TNF)-alpha and TNF-related apoptosis-inducing ligand. In primary adult rat myocyte culture, hypoxia and reoxygenation caused a marked increase in sensitivity to the apoptotic effects of CD95 ligand. Isolated hearts from mice lacking functional CD95 (lpr) display marked reduction in cell death after ischemia and reperfusion compared with wild-type controls. These data suggest that CD95/Apo1/Fas is directly involved in cell death after myocardial ischemia. The CD95 system might thus represent a novel target for therapeutic prevention of postischemic cell death in the heart.
ISSN:0009-7322
1524-4539
DOI:10.1161/01.cir.102.8.915