PMID- 19880804
OWN - NLM
STAT- MEDLINE
DCOM- 20100216
LR  - 20211020
IS  - 1941-3297 (Electronic)
IS  - 1941-3289 (Print)
IS  - 1941-3289 (Linking)
VI  - 3
IP  - 1
DP  - 2010 Jan
TI  - The cytoprotective effects of tumor necrosis factor are conveyed through tumor 
      necrosis factor receptor-associated factor 2 in the heart.
PG  - 157-64
LID - 10.1161/CIRCHEARTFAILURE.109.899732 [doi]
AB  - BACKGROUND: Activation of both type 1 and type 2 tumor necrosis factor (TNF) 
      receptors (TNFR1 and TNFR2) confers cytoprotection in cardiac myocytes. Noting 
      that the scaffolding protein TNF receptor-associated factor 2 (TRAF2) is common 
      to both TNF receptors, we hypothesized that the cytoprotective responses of TNF 
      were mediated through TRAF2. METHODS AND RESULTS: Mice with cardiac-restricted 
      overexpression of low levels of TNF (MHCsTNF(3)) and TRAF2 (MHC-TRAF2(LC)) and 
      mice lacking TNFR1, TNFR2, and TNFR1/TNFR2 were subjected to ischemia (30 
      minutes) reperfusion (30 minutes) injury ex vivo using a Langendorff apparatus. 
      MHCsTNF(3) mice were protected against ischemia-reperfusion injury as shown by a 
      significant approximately 30% greater left ventricular developed pressure, 
      approximately 80% lower creatine kinase release, and Evans blue dye uptake 
      compared with littermates. The extent of ischemia-reperfusion induced injury was 
      similar in wild-type, TNFR1, and TNFR2 deficient mice; however, mice lacking 
      TNFR1/TNFR2 had a significant approximately 40% lower left ventricular developed 
      pressure, a approximately 65% greater creatine kinase release, and approximately 
      40% greater Evans blue dye uptake compared with littermates. Interestingly, 
      MHC-TRAF2(LC) mice had a significant approximately 50% lower left ventricular 
      developed pressure, a approximately 70% lower creatine kinase release, and 
      approximately 80% lower Evans blue dye uptake compared with littermate controls 
      after ischemia-reperfusion injury. Biochemical analysis of the MHC-TRAF2(LC) 
      hearts showed that there was activation of nuclear factor-kappaB but not c-Jun 
      N-terminal kinase activation. CONCLUSIONS: Taken together, these results suggest 
      that TNF confers cytoprotection in the heart through TRAF2-mediated activation of 
      nuclear factor-kappaB.
FAU - Burchfield, Jana S
AU  - Burchfield JS
AD  - Center for Cardiovascular Research, Division of Cardiology, Department of 
      Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
FAU - Dong, Jian-Wen
AU  - Dong JW
FAU - Sakata, Yasushi
AU  - Sakata Y
FAU - Gao, Feng
AU  - Gao F
FAU - Tzeng, Huei-Ping
AU  - Tzeng HP
FAU - Topkara, Veli K
AU  - Topkara VK
FAU - Entman, Mark L
AU  - Entman ML
FAU - Sivasubramanian, Natarajan
AU  - Sivasubramanian N
FAU - Mann, Douglas L
AU  - Mann DL
LA  - eng
GR  - R01 HL061543/HL/NHLBI NIH HHS/United States
GR  - R01 HL61543/HL/NHLBI NIH HHS/United States
GR  - HL 089792/HL/NHLBI NIH HHS/United States
GR  - R01 HL061543-02/HL/NHLBI NIH HHS/United States
GR  - R01 HL076661/HL/NHLBI NIH HHS/United States
GR  - R01 HL042250/HL/NHLBI NIH HHS/United States
GR  - R01 HL058081-04/HL/NHLBI NIH HHS/United States
GR  - R01 HL058081/HL/NHLBI NIH HHS/United States
GR  - R01 HL-42250/HL/NHLBI NIH HHS/United States
GR  - R01 HL089792-03/HL/NHLBI NIH HHS/United States
GR  - R01 HL58081/HL/NHLBI NIH HHS/United States
GR  - R01 HL089792/HL/NHLBI NIH HHS/United States
GR  - HL 076661/HL/NHLBI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20091030
PL  - United States
TA  - Circ Heart Fail
JT  - Circulation. Heart failure
JID - 101479941
RN  - 0 (Receptors, Tumor Necrosis Factor, Type II)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - *Heart
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Receptors, Tumor Necrosis Factor, Type II/*metabolism
MH  - Reperfusion Injury/*metabolism
MH  - Signal Transduction
MH  - Tumor Necrosis Factor-alpha/*metabolism
PMC - PMC2910515
MID - NIHMS210260
EDAT- 2009/11/03 06:00
MHDA- 2010/02/17 06:00
PMCR- 2011/01/01
CRDT- 2009/11/03 06:00
PHST- 2009/11/03 06:00 [entrez]
PHST- 2009/11/03 06:00 [pubmed]
PHST- 2010/02/17 06:00 [medline]
PHST- 2011/01/01 00:00 [pmc-release]
AID - CIRCHEARTFAILURE.109.899732 [pii]
AID - 10.1161/CIRCHEARTFAILURE.109.899732 [doi]
PST - ppublish
SO  - Circ Heart Fail. 2010 Jan;3(1):157-64. doi: 10.1161/CIRCHEARTFAILURE.109.899732. 
      Epub 2009 Oct 30.