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Circulation. 2014 Sep 9;130(11):902-9. doi: 10.1161/CIRCULATIONAHA.114.009683. Epub 2014 Jun 30.

PTP1b is a physiologic regulator of vascular endothelial growth factor signaling in endothelial cells.

Author information

  • 1From the Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine (A.A.L., D.L., A.D., J.Z., Z.W.Z., A.E., M.S.) and the Department of Cell Biology (M.S.), Yale University School of Medicine, New Haven, CT.
  • 2From the Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine (A.A.L., D.L., A.D., J.Z., Z.W.Z., A.E., M.S.) and the Department of Cell Biology (M.S.), Yale University School of Medicine, New Haven, CT. michael.simons@yale.edu.

Abstract

BACKGROUND:

Regulation of vascular endothelial growth factor receptor-2 (VEGFR2) signaling is a control point that determines the extent of vascular tree formation. Recent studies demonstrated an important role played by VEGFR2 endothelial trafficking in control of its activity and suggested the involvement of a phosphotyrosine phosphatase 1b (PTP1b) in this process. This study was designed to define the role of PTP1b in endothelial VEGFR2 signaling and its role in regulation of angiogenesis and arteriogenesis.

METHODS AND RESULTS:

We generated mice carrying an endothelial-specific deletion of PTP1b and examined the effect of this knockout on VEGF signaling, angiogenesis, and arteriogenesis in vitro and in vivo. PTP1b knockout endothelial cells had increased VEGF-dependent activation of extracellular signal-regulated kinase signaling, sprouting, migration, and proliferation compared with controls. Endothelial PTP1b null mice had increased retinal and Matrigel implant angiogenesis and accelerated wound healing, pointing to enhanced angiogenesis. Increased arteriogenesis was demonstrated by observations of faster recovery of arterial blood flow and large numbers of newly formed arterioles in the hindlimb ischemia mouse model. PTP1b endothelial knockout also rescued impaired blood flow recovery after common femoral artery ligation in synectin null mice.

CONCLUSIONS:

PTP1b is a key regulator of endothelial VEGFR2 signaling and plays an important role in regulation of the extent of vascular tree formation.

© 2014 American Heart Association, Inc.

KEYWORDS:

PTP1b; VEGF; VEGF receptor-2; angiogenesis; arteriogenesis; extracellular signal-regulated kinases

PMID:
24982127
[PubMed - indexed for MEDLINE]
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