title: Regulatory T cells contribute to rosuvastatin-induced cardioprotection against ischemia-reperfusion injury.
abstract: OBJECTIVE
  CD4CD25 regulatory T cells (Tregs) play a key role in the prevention of various inflammatory and autoimmune disorders by suppressing immune responses. The beneficial effect of statins on myocardial ischemia-reperfusion injury (IRI) depends in part on their immunomodulatory and anti-inflammatory mechanisms. We aimed to determine whether Tregs contribute to statin-induced cardioprotection against myocardial IRI.
  
  
  METHODS
  Thirty-two rats were divided into four groups: sham, ischemia-reperfusion (IR), rosuvastatin (RSV)/IR, and mevalonic acid (MVA)+RSV/IR. Myocardial IR was induced by a 30-min coronary occlusion, followed by a 48-h reperfusion. RSV (5 mg/kg) was administered intravenously 18 h before IR. The rats were killed after 48-h reperfusion. Serum cardiac troponin I (cTnI) was measured by ELISA, infiltration of inflammatory cells in myocardium by hematoxylin and eosin staining, expression of FoxP3 protein by western blotting, accumulation of Tregs in myocardium by immunohistochemical examination, and infarct size by TTC staining.
  
  
  RESULTS
  Significant elevation in serum cTnI, enlarged infarct size, and marked infiltration of inflammatory cells in myocardium were observed in the IR group. The administration of RSV significantly reduced the serum cTnI level, attenuated the accumulation of inflammatory cells, decreased infarct size, and increased the FoxP3 expression and Treg accumulation in myocardium compared with the IR group. The combination of RSV and MVA pretreatment partially abolished the anti-inflammatory and infarct size-limiting effects and completely reversed Treg accumulation in myocardium induced by RSV. The accumulation of inflammatory cells was negatively correlated with FoxP3 expression and Treg accumulation in the ischemic myocardium.
  
  
  CONCLUSIONS
  RSV pretreatment was associated with more Treg accumulation, less inflammatory response, and myocardial injury, suggesting that such cardioprotection against IRI was partially mediated by Treg-negative modulation of inflammation response, probably through the HMG-CoA reductase pathway.
authors.affiliation: Department of Coronary Artery Disease, Union Hospital, Union Clinic Medical College, Fujian Medical University, Fuzhou, People's Republic of 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: Zhaoyang
authors.initials: Z
authors.lastname: Chen
authors.forename: Lianglong
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D005464:Fluorobenzenes / Q000494:pharmacology*; D051858:Forkhead Transcription Factors / Q000187:drug effects / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008297:Male; D008798:Mevalonic Acid / Q000494:pharmacology; D017202:Myocardial Ischemia / Q000276:immunology*; D015428:Myocardial Reperfusion Injury / Q000276:immunology* / Q000517:prevention & control; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D019210:Troponin I / Q000187:drug effects / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; D005464:Fluorobenzenes; D051858:Forkhead Transcription Factors; C500522:Foxp3 protein, rat; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D019210:Troponin I; D000068718:Rosuvastatin Calcium; D008798:Mevalonic Acid