title: Accelerated vascular aging in CuZnSOD-deficient mice: impact on EPC function and reparative neovascularization.
abstract: OBJECTIVE
  Aging is associated with increased oxidative stress levels and impaired neovascularization following ischemia. CuZnSOD has an important role to limit oxidative stress in the vasculature. Here we investigated the role of CuZnSOD for the modulation of ischemia-induced neovascularisation during aging.
  
  
  RESULTS
  Hindlimb ischemia was surgically induced in young (2- month-old) or older (8-month-old) wild type (WT) and CuZnSOD(-/-) mice. We found that blood flow recovery after ischemia and vascular density in ischemic muscles were significantly reduced in older compared to young WT mice. Both in young and older mice, CuZnSOD deficiency led to a further reduction of neovascularization. Accordingly, the resulting neovascularisation potential in a young CuZnSOD(-/-) mouse was similar to that of an older WT mouse. Oxidative stress levels were also increased to similar levels in the ischemic muscles of young CuZnSOD(-/-) and older WT mice. To identify potential mechanisms involved, we investigated the effect of aging and CuZnSOD deficiency on the number and the function of endothelial progenitor cells (EPCs). Both aging and CuZnSOD deficiency were associated with reduced number of bone marrow and peripheral EPCs. The effect of moderate aging alone on specific functional activities of EPCs (migration, integration into tubules) was modest. However, CuZnSOD deficiency was associated with severe age-dependent defects in EPC functional activities.
  
  
  CONCLUSIONS
  CuZnSOD deficiency is associated with accelerated vascular aging and impaired ischemia-induced neovascularization. Our results suggest that in the context of aging, CuZnSOD has an essential role to protect against excessive oxidative stress in ischemic tissues and preserve the function of EPCs.
authors.affiliation: Department of Cardiovascular Research, Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada.
authors.forename: Jessika
authors.initials: J
authors.lastname: Groleau
authors.forename: Sylvie
authors.initials: S
authors.lastname: Dussault
authors.forename: Julie
authors.initials: J
authors.lastname: Turgeon
authors.forename: Paola
authors.initials: P
authors.lastname: Haddad
authors.forename: Alain
authors.initials: A
authors.lastname: Rivard
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D002452:Cell Count; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism / Q000502:physiology*; D005260:Female; D005434:Flow Cytometry; D006614:Hindlimb / Q000098:blood supply; D006801:Humans; D007150:Immunohistochemistry; D007511:Ischemia / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000502:physiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology; D013482:Superoxide Dismutase / Q000172:deficiency* / Q000235:genetics; D013481:Superoxides / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D013481:Superoxides; D013482:Superoxide Dismutase