title: Innate immune response after acute myocardial infarction and pharmacomodulatory action of tacrolimus in reducing infarct size and preserving myocardial integrity.
abstract: BACKGROUND
  This study investigated the association between innate immune reaction and myocardial damage after acute myocardial infarction (AMI) and anti-inflammatory role of tacrolimus in reducing infarct size. Male mini-pigs (n=18) were equally categorized into sham control (SC), untreated AMI (by ligation of left anterior descending coronary artery), and AMI-Tacrolimus (AMI-Tac) (0.5 mg intra-coronary injection 30 minutes post-AMI). Cardiac magnetic resonance imaging (MRI) was performed at post-AMI days 2, 5 and 21 before sacrificing the animals.
  
  
  RESULTS
  By post-AMI day 21, left ventricular ejection fraction (LVEF) was lowest in untreated AMI animals, significantly higher in SC than in AMI-Tac group (all p<0.003). Infarct areas at basal, middle, and apical levels, numbers of CD14+ and iNOS+ cells in infarct area (IA) and peri-IA, and protein expression of CD14, CD68, and Ly6g from circulating inflammatory cells showed an opposite pattern compared with that of LVEF in all groups (all p<0.005). Protein expressions of MCP-1, MIP-1, TNF-α, NF-κB, iNOS, and IL-12 in IA and peri-IA exhibited an identical pattern compared to that of CD14, CD68, and Ly6g from circulating inflammatory cells (all p<0.01). Expressions of myocardial damage biomarkers in IA and peri-IA [γ-H2AX, β-myosin heavy chain (MHC), Smad3, TGF-β] were highest in AMI and higher in AMI-Tac than in SC, whereas expressions of myocardial integrity biomarkers (connexin43, mitochondrial cytochrome-C, α-MHC, BMP-2, Smad1/5) were opposite to those of damage biomarkers (all p<0.001).
  
  
  CONCLUSIONS
  Innate immune responses were markedly augmented and LVEF was significantly reduced after AMI but were remarkably improved after tacrolimus treatment.
authors.forename: Jiunn-Jye
authors.initials: JJ
authors.lastname: Sheu
authors.forename: Pei-Hsun
authors.initials: PH
authors.lastname: Sung
authors.forename: Steve
authors.initials: S
authors.lastname: Leu
authors.forename: Han-Tan
authors.initials: HT
authors.lastname: Chai
authors.forename: Yen-Yi
authors.initials: YY
authors.lastname: Zhen
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Chen
authors.forename: Sarah
authors.initials: S
authors.lastname: Chua
authors.forename: Yung-Lung
authors.initials: YL
authors.lastname: Chen
authors.forename: Tzu-Hsien
authors.initials: TH
authors.lastname: Tsai
authors.forename: Fan-Yen
authors.initials: FY
authors.lastname: Lee
authors.forename: Hsueh-Wen
authors.initials: HW
authors.lastname: Chang
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. sfatko@adm.cgmh.org.tw.
authors.forename: Sheung-Fat
authors.initials: SF
authors.lastname: Ko
authors.forename: Hon-Kan
authors.initials: HK
authors.lastname: Yip
mesh_terms: D000818:Animals; D015153:Blotting, Western; D007113:Immunity, Innate / Q000187:drug effects*; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D013552:Swine; D013556:Swine, Miniature; D016559:Tacrolimus / Q000494:pharmacology*; D016277:Ventricular Function, Left
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus