Overexpression of catalase in myeloid cells causes impaired postischemic neovascularization

Roberto Hodara, Daiana Weiss, Giji Joseph, Juan C. Velasquez-Castano, Natalia Landázuri, Ji Woong Han, Young Sup Yoon, W. Robert Taylor

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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. 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 Tg mice, suggesting a role for H2O2 in regulating the ability of macrophages to infiltrate ischemic tissues. CONCLUSION-: MLC-derived H 2O2 plays a key role in promoting neovascularization in response to ischemia and is a necessary factor for the development of ischemia-induced inflammation.

Original languageEnglish
Pages (from-to)2203-2209
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Volume31
Issue number10
DOIs
Publication statusPublished - 2011 Oct 1

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All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Hodara, R., Weiss, D., Joseph, G., Velasquez-Castano, J. C., Landázuri, N., Han, J. W., Yoon, Y. S., & Taylor, W. R. (2011). Overexpression of catalase in myeloid cells causes impaired postischemic neovascularization. Arteriosclerosis, thrombosis, and vascular biology, 31(10), 2203-2209. https://doi.org/10.1161/ATVBAHA.111.233247