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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:1761.)
© 2004 American Heart Association, Inc.

Brief Reviews

Endothelium-Targeted Gene and Cell-Based Therapies for Cardiovascular Disease

Luis G. Melo; Massimiliano Gnecchi; Alok S. Pachori; Deling Kong; Kai Wang; Xiaoli Liu; Richard E. Pratt; Victor J. Dzau

From the Department of Physiology (L.G.M., K.W., X.L.), Queen’s University, Kingston, Ontario, Canada; and the Department of Medicine (L.G.M., M.G., A.S.P., D.K., R.E.P., V.J.D.), Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass.

Correspondence to Dr Luis G. Melo, Department of Physiology, Queen’s University, 18 Stuart Street, Kingston, Ontario, K7L 3N6, Canada. E-mail melol{at}post.queensu.ca

Most common cardiovascular diseases are accompanied by endothelial dysfunction. Because of its predominant role in the pathogenesis of cardiovascular disease, the vascular endothelium is an attractive therapeutic target. The identification of promoter sequences capable of rendering endothelial-specific transgene expression together with the recent development of vectors with enhanced tropism for endothelium may offer opportunities for the design of new strategies for modulation of endothelial function. Such strategies may be useful in the treatment of chronic diseases such as hypertension, atherosclerosis, and ischemic artery disease, as well as in acute myocardial infarction and during open heart surgery for prevention of ischemia and reperfusion (I/R)-induced injury. The recent identification of putative endothelial progenitor cells in peripheral blood may allow the design of autologous cell-based strategies for neovascularization of ischemic tissues and for the repair of injured blood vessels and bioengineering of vascular prosthesis. "Proof-of-concept" for some of these strategies has been established in animal models of cardiovascular disease. However the successful translation of these novel strategies into clinical application will require further developments in vector and delivery technologies. Further characterization of the processes involved in mobilization, migration, homing, and incorporation of endothelial progenitor cells into the target tissues is necessary, and the optimal conditions for therapeutic application of these cells need to be defined and standardized.

Endothelial dysfunction plays a pivotal role in cardiovascular disease. The recent isolation of endothelial progenitor cells together with the availability of promoter sequences and vectors capable of rendering endothelial-specific transgene expression may offer opportunities for the design of novel therapeutic strategies for improvement of endothelial function in cardiovascular disease.

Key Words: endothelial progenitor cells • endothelial-specific expression • gene therapy • targeting • viral vectors

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