This Article Full Text Full Text (PDF) All Versions of this Article: 28/2/290    most recent ATVBAHA.107.158485v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Duvall, C. L. Articles by Taylor, W. R. Search for Related Content PubMed PubMed Citation Articles by Duvall, C. L. Articles by Taylor, W. R. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Substance via MeSH

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:290.)
© 2008 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

The Role of Osteopontin in Recovery from Hind Limb Ischemia

Craig L. Duvall; Daiana Weiss; Scott T. Robinson; Fadi M.F. Alameddine; Robert E. Guldberg; W. Robert Taylor

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.

Correspondence to W. Robert Taylor, MD, PhD, Emory University School of Medicine, Cardiology Division, 1639 Pierce Drive, Suite 319 WMB, Atlanta, GA 30322. E-mail wtaylor{at}emory.edu

Abstract

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.

We investigated the role of osteopontin (OPN) in recovery from hind limb ischemia. OPN^–/– mice exhibited delayed ischemic limb recovery, which may be attributable to defective response of OPN^–/– monocytes/macrophages to chemoattraction. These results provide the first evidence that a role exists for OPN during ischemic limb revascularization in vivo.

Key Words: osteopontin • hind limb ischemia • angiogenesis • arteriogenesis • collateral vessels