Overexpression of catalase in myeloid cells causes impaired postischemic neovascularization

Arterioscler Thromb Vasc Biol. 2011 Oct;31(10):2203-9. doi: 10.1161/ATVBAHA.111.233247. Epub 2011 Jul 28.


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.

Methods and 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Capillaries / diagnostic imaging
  • Capillaries / enzymology*
  • Capillaries / physiopathology
  • Catalase / biosynthesis*
  • Catalase / genetics
  • Cell Movement
  • Cells, Cultured
  • Collateral Circulation
  • Disease Models, Animal
  • Endothelial Cells / metabolism
  • Femoral Artery / surgery
  • Genotype
  • Hindlimb
  • Humans
  • Hydrogen Peroxide / metabolism*
  • Inflammation Mediators / metabolism
  • Ischemia / enzymology*
  • Ischemia / genetics
  • Ischemia / physiopathology
  • Laser-Doppler Flowmetry
  • Ligation
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Motor Activity
  • Muscle, Skeletal / blood supply*
  • Myeloid Cells / enzymology*
  • Neovascularization, Physiologic* / genetics
  • Phenotype
  • RNA, Messenger / metabolism
  • Regional Blood Flow
  • Stem Cells / metabolism
  • Time Factors
  • Ultrasonography
  • Up-Regulation
  • X-Ray Microtomography


  • Inflammation Mediators
  • RNA, Messenger
  • Hydrogen Peroxide
  • Catalase