title: Bone marrow transplantation modulates tissue macrophage phenotype and enhances cardiac recovery after subsequent acute myocardial infarction.
abstract: BACKGROUND
  Bone marrow transplantation (BMT) is commonly used in experimental studies to investigate the contribution of BM-derived circulating cells to different disease processes. During studies investigating the cardiac response to acute myocardial infarction (MI) induced by permanent coronary ligation in mice that had previously undergone BMT, we found that BMT itself affects the remodelling response.
  
  
  RESULTS
  Compared to matched naive mice, animals that had previously undergone BMT developed significantly less post-MI adverse remodelling, infarct thinning and contractile dysfunction as assessed by serial magnetic resonance imaging. Cardiac rupture in male mice was prevented. Histological analysis showed that the infarcts of mice that had undergone BMT had a significantly higher number of inflammatory cells, surviving cardiomyocytes and neovessels than control mice, as well as evidence of significant haemosiderin deposition. Flow cytometric and histological analyses demonstrated a higher number of alternatively activated (M2) macrophages in myocardium of the BMT group compared to control animals even before MI, and this increased further in the infarcts of the BMT mice after MI.
  
  
  CONCLUSIONS
  The process of BMT itself substantially alters tissue macrophage phenotype and the subsequent response to acute MI. An increase in alternatively activated macrophages in this setting appears to enhance cardiac recovery after MI.
authors.affiliation: Cardiovascular Division, King's College London British Heart Foundation Centre of Excellence, London, UK; Division of Imaging Sciences and Bioengineering, King's College London British Heart Foundation Centre of Excellence, London, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Protti
authors.affiliation: Cardiovascular Division, King's College London British Heart Foundation Centre of Excellence, London, UK.
authors.forename: Heloise
authors.initials: H
authors.lastname: Mongue-Din
authors.affiliation: BHF/University Centre for Cardiovascular Science, University of Edinburgh, Queens Medical Research Institute, Edinburgh, UK.
authors.forename: Katie J
authors.initials: KJ
authors.lastname: Mylonas
authors.affiliation: Cardiovascular Division, King's College London British Heart Foundation Centre of Excellence, London, UK.
authors.forename: Alexander
authors.initials: A
authors.lastname: Sirker
authors.affiliation: Cardiovascular Division, King's College London British Heart Foundation Centre of Excellence, London, UK; Department of Cardiology, Universitätsklinikum Regensburg, Germany.
authors.forename: Can Martin
authors.initials: CM
authors.lastname: Sag
authors.affiliation: BHF/University Centre for Cardiovascular Science, University of Edinburgh, Queens Medical Research Institute, Edinburgh, UK.
authors.forename: Megan M
authors.initials: MM
authors.lastname: Swim
authors.affiliation: Department of Cardiology, Universitätsklinikum Regensburg, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Maier
authors.affiliation: Cardiovascular Division, King's College London British Heart Foundation Centre of Excellence, London, UK.
authors.forename: Greta
authors.initials: G
authors.lastname: Sawyer
authors.affiliation: Cardiovascular Division, King's College London British Heart Foundation Centre of Excellence, London, UK.
authors.forename: Xuebin
authors.initials: X
authors.lastname: Dong
authors.affiliation: Division of Imaging Sciences and Bioengineering, King's College London British Heart Foundation Centre of Excellence, London, UK.
authors.forename: Rene
authors.initials: R
authors.lastname: Botnar
authors.affiliation: Department of Histopathology, King's College Hospital, London, UK.
authors.forename: Jon
authors.initials: J
authors.lastname: Salisbury
authors.affiliation: BHF/University Centre for Cardiovascular Science, University of Edinburgh, Queens Medical Research Institute, Edinburgh, UK.
authors.forename: Gillian A
authors.initials: GA
authors.lastname: Gray
authors.affiliation: Cardiovascular Division, King's College London British Heart Foundation Centre of Excellence, London, UK. Electronic address: ajay.shah@kcl.ac.uk.
authors.forename: Ajay M
authors.initials: AM
authors.lastname: Shah
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D003331:Coronary Vessels; D003971:Diastole; D005260:Female; D006341:Heart Rupture / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D006485:Hemosiderin / Q000378:metabolism; D008026:Ligation; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D020127:Recovery of Function; D013318:Stroke Volume; D016019:Survival Analysis; D013599:Systole
chemical_list: D006485:Hemosiderin
keywords: Bone marrow transplantation; Macrophage polarisation; Myocardial infarction