The stimulation of neo-angiogenesis in the ischemic heart by the human growth factor FGF.

ABSTRACT

BACKGROUND: The present article deals with the conduct of our animal experiments with the human growth factor FGF (fibroblast growth factor) and the results obtained therefrom. METHODS: In order to establish the angiogenetic potential of FGF, this factor was first obtained from a genetically transformed strain of E. Coli, and then isolated and highly purified. Afterwards the growth factor FGF has been used in several in vitro- and in vivo experiments in order to prove its influence on neo-angiogenesis in ischemic tissue. RESULTS: In cultures of endothelial cells from the human great saphenous vein it has been possible to stimulate growth successfully with FGF obtained in this way, and a further increase in its action was brought about by the addition of heparin. In tritium-thymidine assays, the endothelial cell stimulating action of FGF was confirmed. It could also be shown angiographically that administering FGF to the ischemic myocardium of these animals initiates the development of new vessels, and we could demonstrate that a myocardial capillary network sprouting directly from the coronary vessels themselves can establish an alternative blood flow. These results were confirmed histologically by the significantly greater capillary density which appeared following the use of the growth factor. CONCLUSIONS: By using the human growth factor FGF, we have been able for the first time to understand the physiological processes of angiogenesis as they come into play during wound healing or the development of collaterals following tissue ischemia, and to use this knowledge for the production of new vessels in the ischemic hearts of rats and rabbits. Decisive for the future use of the factor in human patients -- particularly for the treatment of coronary heart disease (CHD) are the results of experimental investigations designed to exclude the possibility of the growth factor initiating or stimulating neoplasia.