Efficacy of systemic administration of SDF-1 in a model of vascular insufficiency: support for an endothelium-dependent mechanism.

Published

Journal Article

OBJECTIVE: Studies have reported that administration of stromal cell-derived factor-1 (SDF-1), the ligand for the G-protein coupled receptor CXCR4, increased collateral blood flow in a mouse model of vascular insufficiency via recruitment of endothelial precursor cells (EPC). The present study investigated the contribution of mature endothelial cells in the actions of SDF-1. METHODS: The regulation of SDF-1 and CXCR4 was examined in the rat cornea cauterization (CC) and aortic ring (AR) model. The functional significance of the SDF-1/CXCR4 pathway was explored in cultured endothelial cells, the AR model, and on collateral blood flow in a rat model of vascular insufficiency. RESULTS: In the present study, the CXCR4 transcript was dramatically upregulated in the rat CC and AR explants, systems containing and lacking bone marrow-derived EPCs, respectively. Addition of AMD3100, a selective CXCR4 antagonist, had no effect on vessel growth in the AR alone, but completely inhibited SDF-1 mediated increases in vascular sprouting. In cultured endothelial cells, SDF-1 alone or in combination with vascular endothelial growth factor (VEGF) significantly enhanced cell survival and migration. Finally, systemic administration of SDF-1 in a rat model of arterial insufficiency enhanced collateral blood flow above vehicle control and equal to that of VEGF after 2 weeks of treatment. CONCLUSION: These studies support activation of the SDF-1/CXCR4 axis as a means to promote blood vessel growth and enhance collateral blood flow, at least in part, via direct effects on vascular endothelial cells.

Full Text

Duke Authors

Cited Authors

  • Carr, AN; Howard, BW; Yang, HT; Eby-Wilkens, E; Loos, P; Varbanov, A; Qu, A; DeMuth, JP; Davis, MG; Proia, A; Terjung, RL; Peters, KG

Published Date

  • March 1, 2006

Published In

Volume / Issue

  • 69 / 4

Start / End Page

  • 925 - 935

PubMed ID

  • 16409996

Pubmed Central ID

  • 16409996

International Standard Serial Number (ISSN)

  • 0008-6363

Digital Object Identifier (DOI)

  • 10.1016/j.cardiores.2005.12.005

Language

  • eng

Conference Location

  • England