title: Downregulation of adiponectin induced by tumor necrosis factor α is involved in the aggravation of posttraumatic myocardial ischemia/reperfusion injury.
abstract: 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.
  
  
  METHODS
  Laboratory study.
  
  
  METHODS
  University research unit.
  
  
  METHODS
  Male adult adiponectin knockout mice and wild-type mice.
  
  
  METHODS
  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.
  
  
  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.affiliation: Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xián, China.
authors.forename: Shaowei
authors.initials: S
authors.lastname: Liu
authors.forename: Tao
authors.initials: T
authors.lastname: Yin
authors.forename: Xufeng
authors.initials: X
authors.lastname: Wei
authors.forename: Wei
authors.initials: W
authors.lastname: Yi
authors.forename: Yan
authors.initials: Y
authors.lastname: Qu
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Rutao
authors.initials: R
authors.lastname: Wang
authors.forename: Kun
authors.initials: K
authors.lastname: Lian
authors.forename: Chenhai
authors.initials: C
authors.lastname: Xia
authors.forename: Haifeng
authors.initials: H
authors.lastname: Pei
authors.forename: Lu
authors.initials: L
authors.lastname: Sun
authors.forename: Yanzhuo
authors.initials: Y
authors.lastname: Ma
authors.forename: Wayne Bond
authors.initials: WB
authors.lastname: Lau
authors.forename: Erhe
authors.initials: E
authors.lastname: Gao
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Koch
authors.forename: Haichang
authors.initials: H
authors.lastname: Wang
authors.forename: Ling
authors.initials: L
authors.lastname: Tao
mesh_terms: D052242:Adiponectin / Q000378:metabolism* / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D004195:Disease Models, Animal; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D000068800:Etanercept; D007074:Immunoglobulin G / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000209:etiology / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000209:etiology* / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D011897:Random Allocation; D018124:Receptors, Tumor Necrosis Factor; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology; D014947:Wounds and Injuries / Q000150:complications*
chemical_list: D052242:Adiponectin; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D009569:Nitric Oxide; D000068800:Etanercept