Overexpression of Catalase in Myeloid Cells Causes Impaired Postischemic Neovascularization
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 the chemical identity of the reactive oxygen species remain unknown.
Methods and Results—Transgenic mice with MLC-specific overexpression of catalase (TgCat-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 TgCat-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 TgCat-MLC mice, suggesting a role for H2O2 in regulating the ability of macrophages to infiltrate ischemic tissues.
Conclusion—MLC-derived H2O2 plays a key role in promoting neovascularization in response to ischemia and is a necessary factor for the development of ischemia-induced inflammation.
- Received March 3, 2011.
- Accepted July 18, 2011.
- © 2011 American Heart Association, Inc.