PMID- 25888509
OWN - NLM
STAT- MEDLINE
DCOM- 20150921
LR  - 20200930
IS  - 1522-1539 (Electronic)
IS  - 0363-6135 (Linking)
VI  - 308
IP  - 12
DP  - 2015 Jun 15
TI  - TNF-alpha antagonism ameliorates myocardial ischemia-reperfusion injury in mice by 
      upregulating adiponectin.
PG  - H1583-91
LID - 10.1152/ajpheart.00346.2014 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) antagonism alleviates myocardial 
      ischemia-reperfusion (MI/R) injury. However, the mechanisms by which the 
      downstream mediators of TNF-alpha change after acute antagonism during MI/R remain 
      unclear. Adiponectin (APN) exerts anti-ischemic effects, but it is downregulated 
      during MI/R. This study was conducted to investigate whether TNF-alpha is responsible 
      for the decrease of APN, and whether antagonizing TNF-alpha affects MI/R injury by 
      increasing APN. Male adult wild-type (WT), APN knockout (APN KO) mice, and those 
      with cardiac knockdowns of APN receptors via siRNA injection were subjected to 30 
      min of MI followed by reperfusion. The TNF-alpha antagonist etanercept or globular 
      domain of APN (gAD) was injected 10 min before reperfusion. Etanercept 
      ameliorated MI/R injury in WT mice as evidenced by improved cardiac function, and 
      reduced infarct size and cardiomyocyte apoptosis. APN concentrations were 
      augmented in response to etanercept, followed by an increase in AMP-activated 
      protein kinase phosphorylation. Etanercept still increased cardiac function and 
      reduced infarct size and apoptosis in both APN KO and APN receptors knockdown 
      mice. However, its potential was significantly weakened in these mice compared 
      with the WT mice. TNF-alpha is responsible for the decrease in APN during MI/R. The 
      cardioprotective effects of TNF-alpha neutralization are partially due to the 
      upregulation of APN. The results provide more insight into the TNF-alpha-mediated 
      signaling effects during MI/R and support the need for clinical trials to 
      validate the efficacy of acute TNF-alpha antagonism in the treatment of MI/R injury.
CI  - Copyright (c) 2015 the American Physiological Society.
FAU - Gao, Chao
AU  - Gao C
AD  - Department of Cardiology, Xijing Hospital, The Fourth Military Medical 
      University, Xi'an, China;
FAU - Liu, Yi
AU  - Liu Y
AD  - Department of Cardiology, Xijing Hospital, The Fourth Military Medical 
      University, Xi'an, China;
FAU - Yu, Qiujun
AU  - Yu Q
AD  - Department of Cardiology, Xijing Hospital, The Fourth Military Medical 
      University, Xi'an, China;
FAU - Yang, Qiang
AU  - Yang Q
AD  - Department of Cardiology, Xijing Hospital, The Fourth Military Medical 
      University, Xi'an, China;
FAU - Li, Bing
AU  - Li B
AD  - Department of Dermatology, Xijing Hospital, The Fourth Military Medical 
      University, Xi'an, China;
FAU - Sun, Lu
AU  - Sun L
AD  - Department of Cardiology, Xijing Hospital, The Fourth Military Medical 
      University, Xi'an, China;
FAU - Yan, Wenjun
AU  - Yan W
AD  - Department of Cardiology, Xijing Hospital, The Fourth Military Medical 
      University, Xi'an, China;
FAU - Cai, Xiaoqing
AU  - Cai X
AD  - Department of Physiology, The Fourth Military Medical University, Xi'an, China; 
      and.
FAU - Gao, Erhe
AU  - Gao E
AD  - Department of Physiology, The Fourth Military Medical University, Xi'an, China; 
      and Department of Physiology, The Fourth Military Medical University, Xi'an, 
      China; and.
FAU - Xiong, Lize
AU  - Xiong L
AD  - Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical 
      University, Xi'an, China;
FAU - Wang, Haichang
AU  - Wang H
AD  - Department of Cardiology, Xijing Hospital, The Fourth Military Medical 
      University, Xi'an, China;
FAU - Tao, Ling
AU  - Tao L
AD  - Department of Cardiology, Xijing Hospital, The Fourth Military Medical 
      University, Xi'an, China; lingtao2006@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150417
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Adiponectin)
RN  - 0 (Adipoq protein, mouse)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Protective Agents)
RN  - 0 (Receptors, Adiponectin)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (adiponectin receptor 1, mouse)
RN  - 0 (adiponectin receptor 2, mouse)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - OP401G7OJC (Etanercept)
SB  - IM
MH  - AMP-Activated Protein Kinases/metabolism
MH  - Adiponectin/deficiency/genetics/*metabolism
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Cytoprotection
MH  - Disease Models, Animal
MH  - Etanercept
MH  - Immunoglobulin G/*pharmacology
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Myocardial 
      Infarction/genetics/immunology/metabolism/pathology/physiopathology/*prevention & 
      control
MH  - Myocardial Reperfusion 
      Injury/genetics/immunology/metabolism/pathology/physiopathology/*prevention & 
      control
MH  - Myocardium/immunology/*metabolism/pathology
MH  - Phosphorylation
MH  - Protective Agents/*pharmacology
MH  - Receptors, Adiponectin/genetics/metabolism
MH  - Receptors, Tumor Necrosis Factor
MH  - Time Factors
MH  - Tumor Necrosis Factor-alpha/*antagonists & inhibitors/immunology/metabolism
MH  - Up-Regulation
OTO - NOTNLM
OT  - adiponectin knockout mice
OT  - etanercept
OT  - globular domain of adiponectin
EDAT- 2015/04/19 06:00
MHDA- 2015/09/22 06:00
CRDT- 2015/04/19 06:00
PHST- 2014/05/20 00:00 [received]
PHST- 2015/03/23 00:00 [accepted]
PHST- 2015/04/19 06:00 [entrez]
PHST- 2015/04/19 06:00 [pubmed]
PHST- 2015/09/22 06:00 [medline]
AID - ajpheart.00346.2014 [pii]
AID - 10.1152/ajpheart.00346.2014 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2015 Jun 15;308(12):H1583-91. doi: 
      10.1152/ajpheart.00346.2014. Epub 2015 Apr 17.