Publisher Summary The family of fibroblast growth factors (FGF) is the largest family of growth factors involved in soft–tissue growth and regeneration. The FGF family includes seven members that share a varying degree of homology at the protein level and appear to have a similar broad mitogenic spectrum. They are angiogenic and promote the proliferation of a variety of cells of mesodermal and neuroectodermal origin . Three members of the family–namely, K–FGF/HST, FGF–5, INT–2 are identified originally as oncogenes, while two additions, FGF–6 and keratinocyte growth factor (KGF), are isolated by sequence homology or factor purification and cloning. FGF was identified as an activity in pituitary extracts that stimulated the proliferation of 3T3 cells in mice. The two prototypes of basic and acidic protein structure, the FGF genes, and the expressions of FGF are also discussed. FGF consist of three exons, separated by two introns of variable length and FGF genes map on several chromosomes. The molecular regulation of FGF expression, FGF receptors, and their interaction with extracellular matrix is described. The oncogenic potential of FGF members and their involvement in tumors is also discussed. All possible mechanisms operating on the expression of FGFs and their receptors: transcriptional controls, posttranscriptional regulation involving alternative splicing, alternative translation starts resulting in proteins with different properties, and control affecting the secretion of these proteins are discussed.

The FGF family of growth factors and oncogenes.

Coronary collateral vessels reduce damage to ischemic myocardium after coronary obstruction. Factors that stimulate collateral formation are expected to have ameliorating effects on myocardial infarction. In a canine experimental myocardial infarct model, intracoronary injection of basic fibroblast growth factor (bFGF) improved cardiac systolic function and reduced infarct size. Treatment with bFGF increased the number of arterioles and capillaries in the infarct. Thus, the angiogenic action of bFGF might lead to a reduction in infarct size. The application of bFGF might bring about a therapeutic modality for the salvage of infarcted myocardium.

https://science.sciencemag.org/content/sci/257/5075/1401.full.pdf

Salvage of infarcted myocardium by angiogenic action of basic fibroblast growth factor.

Increased coronary blood vessel development could potentially benefit patients with ischemic heart disease. In a model of stress-induced myocardial ischemia, intracoronary injection of a recombinant adenovirus expressing human fibroblast growth factor-5 (FGF-5) resulted in messenger RNA and protein expression of the transferred gene. Two weeks after gene transfer, regional abnormalities in stress-induced function and blood flow were improved, effects that persisted for 12 weeks. Improved blood flow and function were associated with evidence of angiogenesis. This report documents, for the first time, successful amelioration of abnormalities in myocardial blood flow and function following in vivo gene transfer.

Intracoronary gene transfer of fibroblast growth factor-5 increases blood flow and contractile function in an ischemic region of the heart.

R estenosis after percutaneous transluminal coronary angioplasty (PTCA) continues to present a challenge. Multiple therapies, including antiplatelet and anticoagulant agents, calcium antagonists and inhibitors of angiotensin converting enzyme, corticosteroids, endovascular prostheses, atherectomy, fish oil diets, and many other treatments have had only modest effects on the incidence of restenosis.12 These results highlight how little we know of the underlying mechanisms.

Migration of smooth muscle and endothelial cells. Critical events in restenosis.

The fibroblast growth factor family: structural and biological properties.

Acidic and basic fibroblast growth factors (aFGF and bFGF) are angiogenic polypeptide mitogens for cells of mesodermal and neuroectodermal origin. In this report we describe the purification from several normal human hearts (including a very fresh, nonischemic sample) of heparin-binding, acid-, heat- and trypsin-sensitive 14-18-kD peptides that crossreact with antisera against aFGF and bFGF. Further evidence includes (a) prevention of mitogenicity by protamine and by anti-bFGF, (b) displacement of 125I-bFGF from cell membranes, and (c) stimulation of capillary endothelial cell migration. Specific immunohistochemistry localized bFGF to endothelial cells and, surprisingly, to cardiac myocytes, with almost no immunoreactivity in smooth muscle cells. These peptides may function in cardiac embryogenesis, hypertrophy, atherogenesis, angiogenesis, and wound healing, and may also have endocrine, neurotropic, or vasomotor functions.

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M Chiba

Papers

Isolation, characterization, and localization of heparin-binding growth factors in the heart.