© 2000 American Heart Association, Inc.
Editorials |
Fibroblast Growth Factor-1 Stimulates Branching and Survival of Myocardial Arteries
A Goal for Therapeutic Angiogenesis?
From the Center for Transgene Technology & Gene Therapy, University of Leuven, Leuven, Belgium.
Correspondence to P. Carmeliet, MD, PhD, Center for Transgene Technology & Gene Therapy, Campus Gasthuisberg, Herestraat 49, University of Leuven, Leuven, B-3000, Belgium. E-mail peter.carmeliet@med.kuleuven.ac.be
Key Words: angiogenesis • fibroblast growth factor • vascular endothelial growth factor • heart • coronary
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Introduction |
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Fibroblast growth factors (FGFs) were among the first molecules discovered to stimulate the growth of endothelial cells. Now, more than 15 years after their initial discovery,1 we still do not understand what endogenous role they play in embryonic and pathological angiogenesis. Both acidic FGF (FGF-1) and basic FGF (FGF-2) lack a typical secretion signal, their spatiotemporal expressions do not always correlate with active angiogenesis, and genetic loss of either or both growth factors does not cause major vascular defects.2 3 This is in contrast to their effect in stimulating angiogenesis in ischemic myocardium in experimental animal models.4 However, to make matters even more confusing, thus far initial clinical results with FGF-2 in patients have not yielded the expected success in long-term improvement of myocardial perfusion.5 These conflicting data mandate a better understanding of the role of these growth factors in vivo. In this issue of Circulation Research, Fernandez et al6 provide novel in vivo evidence that FGF-1 stimulates the branching of the myocardial arteries. In addition, FGF-1 stimulates the formation of sustainable, functional vessels by preventing their regression. Both effects are attractive, stated goals of therapeutic angiogenesis in ischemic heart disease.
The three-dimensional organization of the vascular network has
fascinated many scientists for a long time. Aristotle, one of the first
of these scientists, wrote, "the system of blood vessels in the body
may be compared with those of water-courses which are constructed in
gardens: they start from one source, or spring, and branch off into
numerous channels, and then
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