title: Targeted deletion of regulatory T cells attenuates the protective effects of myocardial ischemic preconditioning in rats.
abstract: BACKGROUND
  Myocardial ischemia-reperfusion injury (IRI) is associated with activation of the innate immune system and the resultant inflammatory response. Myocardial ischemic preconditioning (IPC) is the most powerful endogenous protective mechanism against myocardial IRI, probably via the role of anti-inflammation. Regulatory T cells (Tregs), which are characterized by the expression of the forkhead/winged-helix transcription factor FoxP3, play an important role in the negative modulation of immune responses. We tested the hypothesis that Tregs may contribute to the protective effect of myocardial IPC through anti-inflammatory mechanisms.
  
  
  RESULTS
  The left anterior descending coronary arteries of rats were occluded for a 30-min ischemia, followed by a 48-h reperfusion. Myocardial IPC was induced by 4 cycles of 5-min ischemia and 5-min reperfusion. Ischemia was achieved by ligation of the left anterior descending coronary artery (LAD), and reperfusion was initiated by releasing the ligature. Rats were injected with a Treg cell-depleting antibody or normal rat immunoglobulin (IgG), after IPC. The accumulation of Tregs was observed at indexed time points following IPC. The protein expression of FoxP3 significantly increased in the myocardium after IPC, and peaked at day-2. Treatment of preconditioned rats with the Treg cell-depleting antibody demonstrated less protein expression of FoxP3 (p < 0.001), more infiltration of inflammatory cells in the myocardium (p < 0.01), and larger myocardial infarct size (p < 0.001), compared with the IgG injection group.
  
  
  CONCLUSIONS
  Cardioprotection by IPC is associated with Tregs.
authors.affiliation: Department of Cardiology, Fujian Provincial Corps Hospital, Chinese People's Armed Police Forces , Fuzhou , P. R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Ke
authors.forename: Jun
authors.initials: J
authors.lastname: Fang
authors.forename: Lin
authors.initials: L
authors.lastname: Fan
authors.forename: Lianglong
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007113:Immunity, Innate / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000037:antagonists & inhibitors* / Q000276:immunology; D019157:Ischemic Preconditioning, Myocardial; D008212:Lymphocyte Depletion / Q000379:methods*; D008297:Male; D009203:Myocardial Infarction / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D017208:Rats, Wistar; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D015415:Biomarkers; D051858:Forkhead Transcription Factors; C500522:Foxp3 protein, rat; D018836:Inflammation Mediators; D053645:Interleukin-2 Receptor alpha Subunit
keywords: cardioprotection; immune cell; inflammation; ischemia; reperfusion