Abstract
Fibroblast growth factors (FGFs) have been applied in a variety of therapeutic and experimental studies to improve collateral blood flow. However, the pathophysiological role and the temporospatial expression of the FGFs and their receptors during arteriogenesis have never been elucidated in vivo. Here, we report that collateral artery growth in its early phase is associated with an increased expression of FGF receptor-1 (FGFR-1) and syndecan-4 on mRNA and protein levels as well as with an increased kinase activity of FGFR-1 in a rabbit model of arteriogenesis. However, the mRNA levels of FGF-1 and -2 remained constant. Our data suggest that these growth factors are supplied by endothelial attracted monocytes that, in turn, produce and deliver the FGFs to growing collateral arteries. Monocyte chemoattractant protein-1-stimulated arteriogenesis was strongly reduced in rabbits by application of the FGF inhibitor polyanetholesulfonic acid, indicating that the monocyte-related arteriogenesis (as well as the unstimulated adaptation proper) is promoted by FGFs. In summary, this study shows that arteriogenesis is associated with an increased expression of the FGFRs at the site of the vessel, whereas the growth-promoting ligands are supplied by monocytes in a paracrine way.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptation, Physiological
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Animals
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Arteries / cytology
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Arteries / growth & development*
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Arteries / metabolism
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Blotting, Western
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Cell Adhesion / drug effects
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Chemokine CCL2 / pharmacology*
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Collateral Circulation
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Female
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Fibroblast Growth Factor 1 / antagonists & inhibitors
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Fibroblast Growth Factor 1 / biosynthesis
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Fibroblast Growth Factor 1 / genetics
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Fibroblast Growth Factor 2 / antagonists & inhibitors
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Fibroblast Growth Factor 2 / biosynthesis
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Fibroblast Growth Factor 2 / genetics
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Fibroblast Growth Factors / physiology*
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Kinetics
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Male
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Membrane Glycoproteins / biosynthesis
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Monocytes / drug effects
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Monocytes / physiology
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Muscle, Smooth, Vascular / metabolism
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Proteoglycans / biosynthesis
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RNA, Messenger / biosynthesis
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Rabbits
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Receptor Protein-Tyrosine Kinases / genetics
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Receptor Protein-Tyrosine Kinases / metabolism
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Receptor, Fibroblast Growth Factor, Type 1
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Receptors, Fibroblast Growth Factor / genetics
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Receptors, Fibroblast Growth Factor / metabolism
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Syndecan-4
Substances
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Chemokine CCL2
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Membrane Glycoproteins
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Proteoglycans
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RNA, Messenger
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Receptors, Fibroblast Growth Factor
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Syndecan-4
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Fibroblast Growth Factor 2
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Fibroblast Growth Factor 1
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Fibroblast Growth Factors
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Receptor Protein-Tyrosine Kinases
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Receptor, Fibroblast Growth Factor, Type 1