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Cardiovascular Research 2001 49(3):522-531; doi:10.1016/S0008-6363(00)00216-9
© 2001 by European Society of Cardiology
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Copyright © 2001, European Society of Cardiology

Therapeutic angiogenesis in cardiology using protein formulations

Mark J. Post1,*, Roger Laham, Frank W. Sellke and Michael Simons

Angiogenesis Research Center and Cardiothoracic Surgery Division (FWS), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

* Corresponding author. Tel.:+1-617-667-3790; fax: +1-617-975-5201 mpost{at}caregroup.harvard.edu

Therapeutic angiogenesis in cardiovascular disease aims at improving myocardial function by increasing blood flow to ischemic myocardium that is not amenable to traditional forms of revascularization. Preclinical data have provided proof of the concept that angiogenic growth factors such as fibroblast growth factor 2 (FGF-2) and vascular endothelium growth factor (VEGF) may indeed improve myocardial flow and function when administered in ways that ensure prolonged tissue exposure to these short-lived molecules. Although other cytokines have been shown to enhance angiogenesis in vivo, FGF-2 and VEGF have been most widely studied and may serve as prototype proangiogenic drugs. Currently, several delivery techniques that are clinically applicable are being studied with respect to tissue distribution and retention as well as angiogenic efficacy of FGF-2 and VEGF. Although tissue distribution and retention of FGF-2 after intramyocardial injection compares favorably with other routes of administration, efficacy studies are not yet conclusive. At the same time, different protein- and gene-based formulations are being investigated. Arguments for and against protein and gene therapy are presented, showing that protein-based therapy seems to have advantages over gene therapy at the present time, although continuous efforts should be made to increase the tissue exposure time after a single administration of protein. While delivery systems and growth factor formulations are being improved, double-blind, placebo-controlled trials designed with existing animal data in mind, are needed to firmly establish the utility of therapeutic angiogenesis in cardiovascular disease.

KEYWORDS Angiogenisis; Coronory disease

1 Angiogenesis Research Center, Beth Israel Deaconess Medical Center, Room SL 423 330 Brookline Ave, Boston, MA, USA 02215.


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