Efficacy of systemic administration of SDF-1 in a model of vascular insufficiency: support for an endothelium-dependent mechanism
- PMID: 16409996
- DOI: 10.1016/j.cardiores.2005.12.005
Efficacy of systemic administration of SDF-1 in a model of vascular insufficiency: support for an endothelium-dependent mechanism
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.
Similar articles
-
Stromal cell-derived factor-1 binding to its chemokine receptor CXCR4 on precursor cells promotes the chemotactic recruitment, development and survival of human osteoclasts.Bone. 2005 May;36(5):840-53. doi: 10.1016/j.bone.2005.01.021. Epub 2005 Mar 24. Bone. 2005. PMID: 15794931
-
Stromal cell-derived factor 1/CXCR4 signaling is critical for the recruitment of mesenchymal stem cells to the fracture site during skeletal repair in a mouse model.Arthritis Rheum. 2009 Mar;60(3):813-23. doi: 10.1002/art.24330. Arthritis Rheum. 2009. PMID: 19248097
-
Combination of stromal-derived factor-1alpha and vascular endothelial growth factor gene-modified endothelial progenitor cells is more effective for ischemic neovascularization.J Vasc Surg. 2009 Sep;50(3):608-16. doi: 10.1016/j.jvs.2009.05.049. Epub 2009 Jul 12. J Vasc Surg. 2009. PMID: 19595531
-
Platelets and stromal cell-derived factor-1 in progenitor cell recruitment.Semin Thromb Hemost. 2007 Mar;33(2):159-64. doi: 10.1055/s-2007-969029. Semin Thromb Hemost. 2007. PMID: 17340464 Review.
-
Role of chemokines in angiogenesis: CXCL12/SDF-1 and CXCR4 interaction, a key regulator of endothelial cell responses.Microcirculation. 2003 Jun;10(3-4):359-70. doi: 10.1038/sj.mn.7800200. Microcirculation. 2003. PMID: 12851652 Review.
Cited by
-
Progesterone modulates endothelial progenitor cell (EPC) viability through the CXCL12/CXCR4/PI3K/Akt signalling pathway.Cell Prolif. 2016 Feb;49(1):48-57. doi: 10.1111/cpr.12231. Epub 2016 Jan 27. Cell Prolif. 2016. PMID: 26818151 Free PMC article.
-
Hypoxic Preconditioning Enhances Cellular Viability and Pro-angiogenic Paracrine Activity: The Roles of VEGF-A and SDF-1a in Rat Adipose Stem Cells.Front Cell Dev Biol. 2020 Nov 23;8:580131. doi: 10.3389/fcell.2020.580131. eCollection 2020. Front Cell Dev Biol. 2020. PMID: 33330455 Free PMC article.
-
The SDF-1-CXCR4 signaling pathway: a molecular hub modulating neo-angiogenesis.Trends Immunol. 2007 Jul;28(7):299-307. doi: 10.1016/j.it.2007.05.007. Epub 2007 Jun 7. Trends Immunol. 2007. PMID: 17560169 Free PMC article.
-
Role of endothelial progenitor cells during ischemia-induced vasculogenesis and collateral formation.Microvasc Res. 2010 May;79(3):200-6. doi: 10.1016/j.mvr.2010.01.012. Epub 2010 Feb 6. Microvasc Res. 2010. PMID: 20144623 Free PMC article. Review.
-
Intermittent pneumatic leg compressions enhance muscle performance and blood flow in a model of peripheral arterial insufficiency.J Appl Physiol (1985). 2012 May;112(9):1556-63. doi: 10.1152/japplphysiol.01337.2011. Epub 2012 Feb 23. J Appl Physiol (1985). 2012. PMID: 22362398 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials