Endogenous tumor necrosis factor protects the adult cardiac myocyte against ischemic-induced apoptosis in a murine model of acute myocardial infarction Academic Article uri icon

Overview

MeSH Major

  • Antigens, CD
  • Apoptosis
  • Myocardial Infarction
  • Myocardial Ischemia
  • Myocardium
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha

abstract

  • Previous studies have shown that proinflammatory cytokines, such as tumor necrosis factor (TNF), are expressed after acute hemodynamic overloading and myocardial ischemia/infarction. To define the role of TNF in the setting of ischemia/infarction, we performed a series of acute coronary artery occlusions in mice lacking one or both TNF receptors. Left ventricular infarct size was assessed at 24 h after acute coronary occlusion by triphenyltetrazolium chloride (TTC) staining in wild-type (both TNF receptors present) and mice lacking either the type 1 (TNFR1), type 2 (TNFR2), or both TNF receptors (TNFR1/TNFR2). Left ventricular infarct size as assessed by TTC staining was significantly greater (P < 0.005) in the TNFR1/TNFR2-deficient mice (77.2% +/- 15.3%) when compared with either wild-type mice (46.8% +/- 19.4%) or TNFR1-deficient (47.9% +/- 10.6%) or TNFR2-deficient (41.6% +/- 16.5%) mice. Examination of the extent of necrosis in wild-type and TNFR1/TNFR2-deficient mice by anti-myosin Ab staining demonstrated no significant difference between groups; however, the peak frequency and extent of apoptosis were accelerated in the TNFR1/TNFR2-deficient mice when compared with the wild-type mice. The increase in apoptosis in the TNFR1/TNFR2-deficient mice did not appear to be secondary to a selective up-regulation of the Fas ligand/receptor system in these mice. These data suggest that TNF signaling gives rise to one or more cytoprotective signals that prevent and/or delay the development of cardiac myocyte apoptosis after acute ischemic injury.

publication date

  • May 9, 2000

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC25850

Digital Object Identifier (DOI)

  • 10.1073/pnas.070036297

PubMed ID

  • 10779546

Additional Document Info

start page

  • 5456

end page

  • 61

volume

  • 97

number

  • 10