title: Physical exercise reduces transplant arteriosclerosis in a mouse aorta transplantation model.
abstract: BACKGROUND
  Transplant arteriosclerosis limits long-term outcome after heart transplantation. The underlying mechanism of transplant arteriosclerosis remains alloreactivity, but it is also influenced by nonimmunologic cofactors. Physical exercise has well-established effects on the prevention of native arteriosclerosis. We hypothesized that physical exercise would reduce the development of transplant arteriosclerosis in an allogeneic transplantation setting.
  
  
  METHODS
  Segments of the thoracic aorta from C57.Bl6 (H2b) or C3H.HeJ (H2k) mice were transplanted into the abdominal aortas of CBA.Ca mice (H2k), representing a major or minor alloantigen mismatch, respectively. Three days after surgery, recipient mice were assigned to either the control or physical exercise (consisting of 2 × 45 minutes of treadmill training per day) groups. Transplant arteriosclerosis was assessed and quantified by histology on day 28 after vessel transplantation. Endothelial cell integrity and function in histology sections and peripheral blood was assessed.
  
  
  RESULTS
  All animals developed transplant arteriosclerosis with more severe luminal occlusion in the major alloantigen mismatch setting. Animals undergoing physical exercise developed significantly less severe transplant arteriosclerosis in both the major (P < .0001) and minor (P < .0001) antigen mismatches than their respective control groups without physical exercise. CD31(+) endothelial cells were present in significantly higher numbers in the grafts and circulating in peripheral blood in the exercise groups compared with their respective control. Above that, we found enhanced endothelial nitric oxide synthase-positive cells in both exercise groups compared with the untreated groups (P = .01 and P = .02, respectively).
  
  
  CONCLUSIONS
  Physical exercise has a protective effect against the development of transplant arteriosclerosis. This could be due to enhanced endothelial cell regeneration and function in the graft.
authors.affiliation: Division of Cardiac, Thoracic, Transplantation, and Vascular Surgery, Hannover Medical School, Hanover, Germany. Electronic address: sommer.wiebke@mh-hannover.de.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Sommer
authors.affiliation: Division of Cardiac, Thoracic, Transplantation, and Vascular Surgery, Hannover Medical School, Hanover, Germany.
authors.forename: Ann-Kathrin
authors.initials: AK
authors.lastname: Knöfel
authors.affiliation: Institute of Pathology, Hannover Medical School, Hanover, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Izykowski
authors.affiliation: Division of Cardiac, Thoracic, Transplantation, and Vascular Surgery, Hannover Medical School, Hanover, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Oldhafer
authors.affiliation: Division of Cardiac, Thoracic, Transplantation, and Vascular Surgery, Hannover Medical School, Hanover, Germany.
authors.forename: Murat
authors.initials: M
authors.lastname: Avsar
authors.affiliation: Institute of Pathology, Hannover Medical School, Hanover, Germany.
authors.forename: Danny
authors.initials: D
authors.lastname: Jonigk
authors.affiliation: Division of Cardiac, Thoracic, Transplantation, and Vascular Surgery, Hannover Medical School, Hanover, Germany.
authors.forename: Gregor
authors.initials: G
authors.lastname: Warnecke
authors.affiliation: Division of Cardiac, Thoracic, Transplantation, and Vascular Surgery, Hannover Medical School, Hanover, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Haverich
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D001013:Aorta, Thoracic / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D001161:Arteriosclerosis / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000637:transplantation; D006648:Histocompatibility; D007519:Isoantigens / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D016377:Organ Transplantation / Q000009:adverse effects*; D005082:Physical Exertion; D014184:Transplantation, Homologous
chemical_list: D007519:Isoantigens; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse