Fas pathway is a critical mediator of cardiac myocyte death and MI during ischemia-reperfusion in vivo

Peiyee Lee, Masataka Sata, David J. Lefer, Stephen M. Factor, Kenneth Walsh, Richard N. Kitsis

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161 Citations (Scopus)

Abstract

Fas is a widely expressed cell surface receptor that can initiate apoptosis when activated by its ligand (FasL). Whereas Fas abundance on cardiac myocytes increases in response to multiple pathological stimuli, direct evidence supporting its role in the pathogenesis of heart disease is lacking. Moreover, controversy exists even as to whether Fas activation induces apoptosis in cardiac myocytes. In this study, we show that adenoviral overexpression of FasL, but not β-galactosidase, results in marked apoptosis both in cultures of primary neonatal cardiac myocytes and in the myocardium of intact adult rats. Myocyte killing by FasL is a specific event, because it does not occur in lpr (lymphoproliferative) mice that lack functional Fas. To assess the contribution of the Fas pathway to myocardial infarction (MI) in vivo, lpr mice were subjected to 30 min of ischemia followed by 24 h of reperfusion. Compared with wild-type mice, lpr mice exhibited infarcts that were 62.3% smaller with 63.8% less myocyte apoptosis. These data provide direct evidence that activation of Fas can induce apoptosis in cardiac myocytes and that Fas is a critical mediator of MI due to ischemia-reperfusion in vivo.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume284
Issue number2 53-2
StatePublished - Feb 1 2003

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Cardiac Myocytes
Reperfusion
Ischemia
Myocardial Infarction
Apoptosis
Muscle Cells
Galactosidases
Cell Surface Receptors
Heart Diseases
Myocardium
Ligands

Keywords

  • Apoptosis
  • Death receptor pathway
  • Genetically altered mice

ASJC Scopus subject areas

  • Physiology

Cite this

Fas pathway is a critical mediator of cardiac myocyte death and MI during ischemia-reperfusion in vivo. / Lee, Peiyee; Sata, Masataka; Lefer, David J.; Factor, Stephen M.; Walsh, Kenneth; Kitsis, Richard N.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 284, No. 2 53-2, 01.02.2003.

Research output: Contribution to journalArticle

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