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Author Notes:

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

We thank Dr. Kerry J. Ressler (Emory University) and Dr. Bernard Lassegue (Emory University) for assistance with lentivirus construct design; Viral Vector Core of the Emory Neuroscience NINDS Core Facilities, funded by grant P30NS055077, for providing the lentivirus vector plasmid; and Drs. Yury A. Bochkov and Ann C. Palmenberg (University of Wisconsin – Madison) for providing the pF/R-wt plasmid containing the WT IRES.


Research Funding:

This work was supported by NIH PO1 HL095070, NIH RO1 HL09058, NIH RO1HL062820 and a post-doctoral grant to Alicia N. Lyle from the American Heart Association.


  • Osteopontin
  • Reactive Oxygen Species
  • Ischemia
  • Angiogenesis
  • Collateral Circulation

Reactive Oxygen Species Regulate Osteopontin Expression in a Murine Model of Post-Ischemic Neo-vascularization


Journal Title:

Arteriosclerosis, Thrombosis, and Vascular Biology


Volume 32, Number 6


, Pages 1383-1391

Type of Work:

Article | Post-print: After Peer Review


Objective Previous findings from our laboratory demonstrated that neo-vascularization was impaired in osteopontin (OPN) knockout animals. However, the mechanisms responsible for regulation of OPN expression in the setting of ischemia remain undefined. Therefore, we sought to determine if OPN is upregulated in response to ischemia and hypothesized that H2O2 is a critical component of the signaling mechanism by which OPN expression is upregulated in response to ischemia in vivo. Methods and Results To determine if ischemic injury upregulates OPN, we used a murine model of hind limb ischemia. Femoral artery ligation in C57Bl/6 mice significantly increased OPN expression and H2O2 production. Infusion of C57Bl/6 mice with PEG-catalase (10,000 U/kg/day) or the use of transgenic mice with smooth muscle cell specific catalase overexpression blunted ischemia-induced OPN, suggesting ischemia-induced OPN expression is H2O2-dependent. Decreased H2O2-mediated OPN blunted reperfusion and collateral formation in vivo. In contrast, the overexpression of OPN using lentivirus restored neovascularization. Conclusions Scavenging H2O2 blocks ischemia-induced OPN expression, providing evidence that ischemia-induced OPN expression is H2O2-dependent. Decreased OPN expression impaired neo-vascularization, whereas overexpression of OPN increased angiogenesis, supporting our hypothesis that OPN is a critical mediator of post-ischemic neo-vascularization and a potential novel therapeutic target for inducing new vessel growth.

Copyright information:

© 2012 American Heart Association, Inc.

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