Document Detail


Downregulation of adiponectin induced by tumor necrosis factor α is involved in the aggravation of posttraumatic myocardial ischemia/reperfusion injury.
MedLine Citation:
PMID:  21499085     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
OBJECTIVE:: Recent clinical observations have indicated that nonlethal mechanical trauma significantly increases myocardial infarction risk even in the presence of completely normal coronary arteries. We investigated the molecular mechanisms responsible for exacerbation of ischemic myocardial injury after nonlethal mechanical trauma with a special focus on the role of tumor necrosis factor α and its potential downstream effector adiponectin, a novel adipokine with anti-inflammatory and cardioprotective properties. DESIGN:: Laboratory study. SETTING:: University research unit. SUBJECTS:: Male adult adiponectin knockout mice and wild-type mice. INTERVENTIONS:: The animals were subjected to nonlethal mechanical trauma using the Noble-Collip drum (40 rpm ± 5 mins) followed by myocardial ischemia/reperfusion injury 7 days posttrauma. We also investigated the effects of neutralizing tumor necrosis factor α with etanercept and exogenous adiponectin supplementation on ischemic myocardial injury after trauma. MEASUREMENTS AND MAIN RESULTS:: Trauma significantly sensitized myocardium to ischemia/reperfusion injury as evidenced by increased apoptosis, enlarged infarct size, and decreased cardiac function. Plasma adiponectin concentrations were reduced after traumatic injury (the nadir occurring 3 days posttrauma), an effect abrogated by etanercept-mediated tumor necrosis factor α blockade. The downregulation of adiponectin was accompanied by increased myocardial superoxide and nitric oxide generation and peroxynitrite formation. Both etanercept and exogenous adiponectin supplementation (on day 3 posttrauma or 10 mins before reperfusion on day 7 posttrauma) markedly inhibited oxidative/nitrative stress and ischemia/reperfusion injury in posttraumatic ischemic/reperfused hearts of wild-type mice, whereas only adiponectin supplementation (but not tumor necrosis factor α inhibition) substantially attenuated posttraumatic ischemia/reperfusion injury in adiponectin knockout mice. CONCLUSIONS:: Tumor necrosis factor α-induced downregulation of adiponectin and the resultant enhanced oxidative/nitrative stress are involved in exacerbated posttraumatic ischemic myocardial injury. Therapeutic approaches blocking tumor necrosis factor α production or restoring adiponectin might have prophylactic value against secondary myocardial ischemic injury after a primary nonlethal mechanical trauma.
Authors:
Shaowei Liu; Tao Yin; Xufeng Wei; Wei Yi; Yan Qu; Yi Liu; Rutao Wang; Kun Lian; Chenhai Xia; Haifeng Pei; Lu Sun; Yanzhuo Ma; Wayne Bond Lau; Erhe Gao; Walter J Koch; Haichang Wang; Ling Tao
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-4-14
Journal Detail:
Title:  Critical care medicine     Volume:  -     ISSN:  1530-0293     ISO Abbreviation:  -     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-4-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0355501     Medline TA:  Crit Care Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
From the Departments of Cardiology (SL, TY, YL, RW, KL, CX, HP, LS, YM, HW, LT), Cardiovascular Surgery (XW, WY), and Neurosurgery (YQ), Xijing Hospital, The Fourth Military Medical University, Xi'an, China; and the Department of Emergency Medicine (WBL) and the Center for Translational Medicine (EG, WJK), Thomas Jefferson University, Philadelphia, PA.
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