on November 15, 2007
Published online before print November 15, 2007, doi: 10.1161/ATVBAHA.107.158485
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Submitted on January 14, 2007
Accepted on November 7, 2007
The Role of Osteopontin in Recovery from Hind Limb Ischemia
Craig L. Duvall ;
From the Wallace H. Coulter Department of Biomedical Engineering (C.L.D., S.T.R., R.E.G., W.R.T.), Georgia Institute of Technology and Emory University, Atlanta; the Division of Cardiology, Department of Medicine (D.W., F.M.F.A., W.R.T.), Emory University, Atlanta; Woodruff School of Mechanical Engineering (R.E.G.), Georgia Institute of Technology, Atlanta; and the Veterans Affairs Medical Center (W.R.T.), Decatur, Ga.
* To whom correspondence should be addressed. E-mail: wtaylor{at}emory.edu.
Objective—Osteopontin (OPN) is a highly phosphorylated extracellular matrix glycoprotein that is involved in a diversity of biological processes. In the vascular wall, OPN is produced by monocytes/macrophages, endothelial cells, and smooth muscle cells, and it is thought to mediate adhesion, migration, and survival of these cell types. In this study, we hypothesized that OPN plays a critical role in recovery from limb ischemia.
Methods and Results—We induced hind limb ischemia in wild-type and OPN-/- mice. OPN-/- mice exhibited significantly delayed recovery of ischemic foot perfusion as determined by LDPI, impaired collateral vessel formation as measured using micro-CT, and diminished functional capacity of the ischemic limb. In the aortic ring assay, normal endothelial cell sprouting was found in OPN-/- mice. However, OPN-/- peritoneal monocytes/macrophages were found to possess significantly reduced migration in response to chemoattraction.
Conclusions—This study provides evidence that a definitive biological role exists for OPN during ischemic limb revascularization, and we have suggested that this may be driven by impaired monocyte/macrophage migration in OPN-/- mice. These findings provide the first in vivo evidence that OPN may be a key regulator in postnatal vascular growth.
Key words: osteopontin • hind limb ischemia • angiogenesis • arteriogenesis • collateral vessels
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