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(Circulation Research. 2003;92:561.)
© 2003 American Heart Association, Inc.

Integrative Physiology

Involvement of the Fibroblast Growth Factor System in Adaptive and Chemokine-Induced Arteriogenesis

Elisabeth Deindl, Imo E. Hoefer, Borja Fernandez, Miroslav Barancik, Matthias Heil, Monika Strniskova, Wolfgang Schaper

From the Max-Planck-Institute, Department of Experimental Cardiology (E.D., I.E.H., B.F., M.H., W.S.), Bad Nauheim, Germany, and the Institute for Heart Research, Slovak Academy of Science (M.B., M.S.), Bratislava, Slovak Republic.

Correspondence to Elisabeth Deindl, PhD, Max-Planck-Institute, Department of Experimental Cardiology, Benekestrasse 2, D-61231 Bad Nauheim, Germany. E-mail e.deindl{at}kerckhoff.mpg.de

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.

Key Words: arteriogenesis • fibroblast growth factors • fibroblast growth factor receptor-1 • syndecan-4 • monocytes

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