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Stromal cell–derived factor 1 promotes angiogenesis via a heme oxygenase 1–dependent mechanism
Open accessAbstract
Stromal cell–derived factor 1 (SDF-1) plays a major role in the migration, recruitment, and retention of endothelial progenitor cells to sites of ischemic injury and contributes to neovascularization. We provide direct evidence demonstrating an important role for heme oxygenase 1 (HO-1) in mediating the proangiogenic effects of SDF-1. Nanomolar concentrations of SDF-1 induced HO-1 in endothelial cells through a protein kinase C ζ–dependent and vascular endothelial growth factor–independent mechanism. SDF-1–induced endothelial tube formation and migration was impaired in HO-1–deficient cells. Aortic rings from HO-1−/− mice were unable to form capillary sprouts in response to SDF-1, a defect reversed by CO, a byproduct of the HO-1 reaction. Phosphorylation of vasodilator-stimulated phosphoprotein was impaired in HO-1−/− cells, an event that was restored by CO. The functional significance of HO-1 in the proangiogenic effects of SDF-1 was confirmed in Matrigel plug, wound healing, and retinal ischemia models in vivo. The absence of HO-1 was associated with impaired wound healing. Intravitreal adoptive transfer of HO-1–deficient endothelial precursors showed defective homing and reendothelialization of the retinal vasculature compared with HO-1 wild-type cells following ischemia. These findings demonstrate a mechanistic role for HO-1 in SDF-1–mediated angiogenesis and provide new avenues for therapeutic approaches in vascular repair.
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Angiogenesis as a therapeutic target
Ferrara, N., & Kerbel, R. S. (2005) · Nature · doi:10.1038/nature04483 · Cited by 2,653
Cited by
Mechanisms of Cell Protection by Heme Oxygenase-1
Gozzelino, R., Jeney, V., & Soares, M. P. (2010) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.010909.105600 · Cited by 1,241
Therapeutic strategies for enhancing angiogenesis in wound healing
Veith, A. P., Henderson, K., Spencer, A., Sligar, A. D., & Baker, A. B. (2019) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2018.09.010 · Cited by 1,021
Oxidative stress in normal and impaired wound repair
SCHAFER, M., & WERNER, S. (2008) · Pharmacological Research · doi:10.1016/j.phrs.2008.06.004 · Cited by 902
Cano Sanchez, M., Lancel, S., Boulanger, E., & Neviere, R. (2018) · Antioxidants · doi:10.3390/antiox7080098 · Cited by 574
Heme oxygenase-1 in tumor biology and therapy
Was, H., Dulak, J., & Jozkowicz, A. (2010) · Current Drug Targets · doi:10.2174/1389450111009011551 · Cited by 259
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Metadata
- Authors
- Deshane, J., Chen, S., Caballero, S., Grochot-Przeczek, A., Was, H., Li Calzi, S., Lach, R., Hock, T. D., Chen, B., Hill-Kapturczak, N., Siegal, G. P., Dulak, J., Jozkowicz, A., Grant, M. B., & Agarwal, A.
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2007-03-05
- Volume
- 204
- Issue
- 3
- Pages
- 605-618
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2101580341
- Cited by
- 283
- References
- 1
- FWCI
- 7.90
- Type
- journal article
- Language
- en
- Open access
- green
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- Deshane, J., Chen, S., Caballero, S., Grochot-Przeczek, A., Was, H., Li Calzi, S., Lach, R., Hock, T. D., Chen, B., Hill-Kapturczak, N., Siegal, G. P., Dulak, J., Jozkowicz, A., Grant, M. B., & Agarwal, A. (2007). Stromal cell–derived factor 1 promotes angiogenesis via a heme oxygenase 1–dependent mechanism. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.20061609
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