title: Overexpression of catalase in myeloid cells causes impaired postischemic neovascularization.
abstract: OBJECTIVE
  Myeloid lineage cells (MLCs) such as macrophages are known to play a key role in postischemic neovascularization. However, the role of MLC-derived reactive oxygen species in this process and their specific chemical identity remain unknown.
  
  
  RESULTS
  Transgenic mice with MLC-specific overexpression of catalase (Tg(Cat-MLC) mice) were created on a C57BL/6 background. Macrophage catalase activity was increased 3.4-fold compared with wild-type mice. After femoral artery ligation, laser Doppler perfusion imaging revealed impaired perfusion recovery in Tg(Cat-MLC) mice. This was associated with fewer collateral vessels, as assessed by microcomputed tomography angiography, and decreased capillary density. Impaired functional recovery of the ischemic limb was also evidenced by a 50% reduction in spontaneous running activity. The deficient neovascularization was associated with a blunted inflammatory response, characterized by decreased macrophage infiltration of ischemic tissues, and lower mRNA levels of inflammatory markers, such as tumor necrosis factor-α, osteopontin, and matrix mettaloproteinase-9. In vitro macrophage migration was impaired in Tg(Cat-MLC) mice, suggesting a role for H(2)O(2) in regulating the ability of macrophages to infiltrate ischemic tissues.
  
  
  CONCLUSIONS
  MLC-derived H(2)O(2) plays a key role in promoting neovascularization in response to ischemia and is a necessary factor for the development of ischemia-induced inflammation.
authors.affiliation: Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Hodara
authors.forename: Daiana
authors.initials: D
authors.lastname: Weiss
authors.forename: Giji
authors.initials: G
authors.lastname: Joseph
authors.forename: Juan C
authors.initials: JC
authors.lastname: Velasquez-Castano
authors.forename: Natalia
authors.initials: N
authors.lastname: Landázuri
authors.forename: Ji Woong
authors.initials: JW
authors.lastname: Han
authors.forename: Young-sup
authors.initials: YS
authors.lastname: Yoon
authors.forename: W Robert
authors.initials: WR
authors.lastname: Taylor
mesh_terms: D000818:Animals; D002196:Capillaries / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000503:physiopathology; D002374:Catalase / Q000096:biosynthesis* / Q000235:genetics; D002465:Cell Movement; D002478:Cells, Cultured; D003097:Collateral Circulation; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D005263:Femoral Artery / Q000601:surgery; D005838:Genotype; D006614:Hindlimb; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D007511:Ischemia / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D017078:Laser-Doppler Flowmetry; D008026:Ligation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity; D018482:Muscle, Skeletal / Q000098:blood supply*; D022423:Myeloid Cells / Q000201:enzymology*; D018919:Neovascularization, Physiologic / Q000235:genetics; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D012039:Regional Blood Flow; D013234:Stem Cells / Q000378:metabolism; D013997:Time Factors; D014463:Ultrasonography; D015854:Up-Regulation; D055114:X-Ray Microtomography
chemical_list: D018836:Inflammation Mediators; D012333:RNA, Messenger; D006861:Hydrogen Peroxide; D002374:Catalase