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Author Notes:

Correspondence to: W. Robert Taylor, MD, PhD, Emory University School of Medicine, Cardiology Division, 1639 Pierce Drive, Suite 319 WMB, Atlanta, GA 30322. wtaylor@emory.edu, Phone: 404.727.8921; Fax: 404.727.3330

Disclosures: None.

Subject:

Research Funding:

This work was supported by American Heart Association grant 10POST4360002 to RH and National Institutes of Health grants RO1 HL090584 and P01 HL095070 to WRT

Keywords:

  • limb ischemia
  • reactive oxygen species
  • angiogenesis
  • hydrogen peroxide
  • macrophages

Over-expression of catalase in myeloid cells causes impaired post-ischemic neovascularization

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Journal Title:

Arteriosclerosis, Thrombosis, and Vascular Biology

Volume:

Volume 31, Number 10

Publisher:

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Objective 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. Methods and Results 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. Conclusions 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.

Copyright information:

© 2011 American Heart Association, Inc. All rights reserved.

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