The role of osteopontin in recovery from hind limb ischemia.
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.


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.
Duvall
Craig L
CL
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, USA.
Weiss
Daiana
D
Robinson
Scott T
ST
Alameddine
Fadi M F
FM
Guldberg
Robert E
RE
Taylor
W Robert
WR
D000818:Animals; D042783:Endothelial Cells / Q000502:physiology*; D006614:Hindlimb / Q000098:blood supply; D007511:Ischemia / Q000503:physiopathology*; D035002:Lower Extremity / Q000098:blood supply* / Q000503:physiopathology; D008264:Macrophages / Q000502:physiology; D008297:Male; D051379:Mice; D018919:Neovascularization, Physiologic / Q000502:physiology*; D053495:Osteopontin / Q000235:genetics / Q000502:physiology*; D020127:Recovery of Function / Q000502:physiology*
C506896:Spp1 protein, mouse; D053495:Osteopontin