Summary

Therapeutic angiogenesis has evolved markedly over the past decade. Although the initial clinical experience has been rather disappointing, the wealth of basic and preclini-cal data strongly suggests that this ultimately will be an effective therapeutic strategy. One novel approach to this therapy that has not yet received vigorous clinical testing involves the use of EPC. This can be achieved either by stimulation of their release (for example, with the use of agents such as GM-CSF) or by physical extraction of such cells from the bone marrow followed by their injection into the target tissues. This and other strategies will undoubtedly be tested in the coming years.

Glossary

Angiogenesis: Growth of capillaries or capillary-like structures (blood vessels with a single endothelial wall layer).

Arteriogenesis: Growth of arterioles or arteries (blood vessels with more than one wall layer).

Gene therapy: Means of transfer of gene encoding for a desired growth factor to a host organism.

Growth factor: A protein capable of induction blood vessel growth. Vasculogenesis: Growth of blood vessels from circulating precursor cells.

Bibliography

Arras, M., Ito, W. D., Scholz, D., Winkler, B., Schaper, J., and Schaper, W. (1998). Monocyte activation in angiogenesis and collateral growth in the rabbit hindlimb. J. Clin. Invest. 101, 40-50. Asahara, T., Murohara, T., Sullivam, A., Silver, M., van der Zee, R., Li, T., Witzenbichler, B., Schatterman, G., and Isner, J. M. (1997). Isolation of putative progenitor endothelial cells for angiogenesis. Science 275, 964-967.

Carmeliet, P. (2003). Angiogenesis in health and disease. Nat. Med. 9, 653-660.

Dor, Y., Djonov, V., Abramovitch, R., Itin, A., Fishman, G. I., Carmeliet, P., Goelman, G., and Keshet, E. (2002). Conditional switching of VEGF provides new insights into adult neovascularization and pro-angiogenic therapy. EMBO J. 21, 1939-1947. First demonstration of the importance of prolonged growth factor expression in maintenance of newly developed vasculature.

Helisch, A., and Schaper, W. (2003). Arteriogenesis: The development and growth of collateral arteries. Microcirculation 10, 83-97. Li, J., Hampton, T., Morgan, J. P., and Simons, M. (1997). Stretch-induced

VEGF expression in the heart. J. Clin. Invest. 100, 18-24. Rafii, S., and Lyden, D. (2003). Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration. Nat. Med. 9, 702-712.

Schultz, A., Lavie, L., Hochberg, I., Beyar, R., Stone, T., Skorecki, K., Lavie, P., Roguin, A., and Levy, A. P. (1999). Interindividual heterogeneity in the hypoxic regulation of VEGF: Significance for the development of the coronary artery collateral circulation. Circulation 100, 547-552. Significance of clinical phenotypes in determining native arteriogenic response to myocardial ischemia. Simons, M., Bonow, R. O., Chronos, N. A., Cohen, D. J., Giordano, F. J., Hammond, H. K., Laham, R. J., Li, W., Pike, M., Sellke, F. W., Stegmann, T. J., Udelson, J. E., and Rosengart, T. K. (2000). Clinical trials in coronary angiogenesis: Issues, problems, consensus: An expert panel summary. Circulation 102, E73-E86. A comprehensive review of issues involving design and execution of clinical trials of therapeutic angiogenesis.

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Capsule Biography

Dr. Simons is Chief of Cardiology and Director of the Angiogenesis Research Center at Dartmouth Medical School. His research activities are centered on endothelial cell matrix interactions and therapeutic angiogene-sis therapies in advanced coronary artery disease.

Dr. Post is Chair of Physiology at the University of Maastricht. His research focuses on ischemic models of angiogenesis and development of growth factor protein and gene delivery tools.

Section E

Vascular Endothelium

Your Heart and Nutrition

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