title: Endogenous tumor necrosis factor protects the adult cardiac myocyte against ischemic-induced apoptosis in a murine model of acute myocardial infarction.
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.
authors.affiliation: Winters Center for Heart Failure Research, Cardiology Section, Veterans Affairs Medical Center, Houston, TX 77030, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Kurrelmeyer
authors.forename: L H
authors.initials: LH
authors.lastname: Michael
authors.forename: G
authors.initials: G
authors.lastname: Baumgarten
authors.forename: G E
authors.initials: GE
authors.lastname: Taffet
authors.forename: J J
authors.initials: JJ
authors.lastname: Peschon
authors.forename: N
authors.initials: N
authors.lastname: Sivasubramanian
authors.forename: M L
authors.initials: ML
authors.lastname: Entman
authors.forename: D L
authors.initials: DL
authors.lastname: Mann
mesh_terms: D000208:Acute Disease; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D017209:Apoptosis; D003331:Coronary Vessels / Q000502:physiology / Q000503:physiopathology; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control*; D017202:Myocardial Ischemia / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000502:physiology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha