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

Citation
I. Jeremias et al., Involvement of CD95/Apo1/Fas in cell death after myocardial ischemia, CIRCULATION, 102(8), 2000, pp. 915-920
Citations number
29
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Journal title
CIRCULATION
ISSN journal
0009-7322 → ACNP
Volume
102
Issue
8
Year of publication
2000
Pages
915 - 920
Database
ISI
SICI code
0009-7322(20000822)102:8<915:IOCICD>2.0.ZU;2-#
Abstract
Background-The death of cardiac cells during ischemia and reperfusion is pa rtially mediated by apoptosis, as seen, eg, in autopsy material of patients after acute myocardial infarction. Methods and Results-To study the role of CD95/Fas/Apol for induction of pos tischemic cell death, we used an ischemia/reperfusion model of isolated rat and mouse hearts in Langendorff perfusion. In this model, caspase-dependen t apoptosis occurred during postischemic reperfusion. Moreover, soluble CD9 5 ligand/Fas ligand was released by the postischemic hearts early after the onset of reperfusion. In addition, this ligand was synthesized de novo und er these circumstances. Similar findings were observed for other "death-ind ucing" ligands, such as tumor necrosis factor (TNF)-alpha and TNF-related a poptosis-inducing ligand. In primary adult rat myocyte culture, hypoxia and reoxygenation caused a marked increase in sensitivity to the apoptotic eff ects of CD95 ligand. Isolated hearts from mice lacking functional CD95 ([pl ) display marked reduction in cell death after ischemia and reperfusion com pared with wild-type controls. Conclusions-These data suggest that CD95/Apol/Fas is directly involved in c ell death after myocardial ischemia. The CD95 system might thus represent a novel target for therapeutic prevention of postischemic cell death in the heart.