Therapeutic angiogenesis in cardiology using protein formulations

Therapeutic angiogenesis in cardiovascular disease aims at improving myocar dial function by increasing blood How to ischemic myocardium that is not am enable to traditional forms of revascularization. preclinical data have pro vided proof of the concept that angiogenic growth factors such as fibroblas t 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 applicab le are being studied with respect to tissue distribution and retention as w ell as angiogenic efficacy of FGF-2 and VEGF. Although tissue distribution and retention of FGF-2 after intramyocardial injection compares favorably w ith other routes of administration, efficacy studies are not yet conclusive . At the same time, different protein- and gene-based formulations are bein g investigated. Arguments for and against protein and gene therapy are pres ented, showing that protein-based therapy seems to have advantages over gen e therapy Lit the present time. although continuous efforts should be made to increase the tissue exposure time after a single administration of prote in. While delivery systems and growth factor formulations are being improve d. double-blind, placebo-controlled trials designed with existing animal da ta in mind, are needed to firmly establish the utility of therapeutic angio genesis in cardiovascular disease. (C) 2001 Elsevier Science B.V. AII right s reserved.