| Autor: |
Carr, Andrew N., Howard, Brian W., Yang, Hsiao T., Eby-Wilkens, Elaine, Loos, Paula, Varbanov, Alex, Qu, Angela, DeMuth, Jeffrey P., Davis, Michael G., Proia, Alan, Terjung, Ronald L., Peters, Kevin G. |
| Předmět: |
|
| Zdroj: |
Cardiovascular Research; Mar2006, Vol. 69 Issue 4, p925-935, 11p |
| Abstrakt: |
Abstract: 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. [Copyright &y& Elsevier] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
