Overexpression of catalase in myeloid cells causes impaired postischemic neovascularization.
Overexpression of catalase in myeloid cells causes impaired postischemic neovascularization.
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DOI：
10.1161/atvbaha.111.233247
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发表时间：
2011-10
期刊：
影响因子：
--
通讯作者：
Taylor WR
中科院分区：
文献类型：
--
作者：
Hodara R;Weiss D;Joseph G;Velasquez-Castano JC;Landázuri N;Han JW;Yoon YS;Taylor WR
Myeloid lineage cells (MLCs) such as macrophages are known to play a key role in post-ischemic neovascularization. However, the role of MLC-derived reactive oxygen species (ROS) in this process and the chemical identity of the ROS remain unknown. Transgenic mice with MLC-specific over-expression of catalase (TgCat-MLC mice) were created on a C57BL/6 background. Macrophage catalase activity was increased 3.4-fold compared to 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 micro CT 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. 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.
