title: Atorvastatin at reperfusion reduces myocardial infarct size in mice by activating eNOS in bone marrow-derived cells.
abstract: BACKGROUND
  The current study was designed to test our hypothesis that atorvastatin could reduce infarct size in intact mice by activating eNOS, specifically the eNOS in bone marrow-derived cells. C57BL/6J mice (B6) and congenic eNOS knockout (KO) mice underwent 45 min LAD occlusion and 60 min reperfusion. Chimeric mice, created by bone marrow transplantation between B6 and eNOS KO mice, underwent 40 min LAD occlusion and 60 min reperfusion. Mice were treated either with vehicle or atorvastatin in 5% ethanol at a dose of 10 mg/kg IV 5 min before initiating reperfusion. Infarct size was evaluated by TTC and Phthalo blue staining.
  
  
  RESULTS
  Atorvastatin treatment reduced infarct size in B6 mice by 19% (p<0.05). In eNOS KO vehicle-control mice, infarct size was comparable to that of B6 vehicle-control mice (p = NS). Atorvastatin treatment had no effect on infarct size in eNOS KO mice (p = NS). In chimeras, atorvastatin significantly reduced infarct size in B6/B6 (donor/recipient) mice and B6/KO mice (p<0.05), but not in KO/KO mice or KO/B6 mice (p = NS).
  
  
  CONCLUSIONS
  The results demonstrate that acute administration of atorvastatin significantly reduces myocardial ischemia/reperfusion injury in an eNOS-dependent manner, probably through the post-transcriptional activation of eNOS in bone marrow-derived cells.
authors.affiliation: Department of Surgery, University of Virginia Health System, Charlottesville, Virginia, United States of America; Department of Cardiovascular Surgery, Tianjin Medical University General Hospital, Tianjin, P.R. China.
authors.forename: Yikui
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, United States of America; La Jolla Institute for Allergy & Immunology, La Jolla, California, United States of America.
authors.forename: Joel
authors.initials: J
authors.lastname: Linden
authors.affiliation: Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, United States of America; Department of Biomedical Engineering, University of Virginia Health System, Charlottesville, Virginia, United States of America.
authors.forename: Brent A
authors.initials: BA
authors.lastname: French
authors.affiliation: Department of Surgery, University of Virginia Health System, Charlottesville, Virginia, United States of America; Department of Biomedical Engineering, University of Virginia Health System, Charlottesville, Virginia, United States of America.
authors.forename: Zequan
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000818:Animals; D000069059:Atorvastatin / Q000494:pharmacology* / Q000627:therapeutic use; D001854:Bone Marrow Cells / Q000201:enzymology; D016026:Bone Marrow Transplantation; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D004789:Enzyme Activation; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000201:enzymology* / Q000276:immunology / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000276:immunology / Q000517:prevention & control*; D020556:Neutrophil Infiltration; D052250:Nitric Oxide Synthase Type III / Q000235:genetics* / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; D000069059:Atorvastatin; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse