Vascular Cell-Derived Heparan Sulfate Shows Coupled Inhibition of Basic Fibroblast Growth Factor Binding and Mitogenesis in Vascular Smooth Muscle Cells

Basic fibroblast growth factor (bFGF) has been previously shown to be mitogenic for vascular smooth muscle cells (VSMCs) in vivo, but only after vascular injury. We show in the present study that the regulation of bFGF-stimulated VSMC proliferation, by vascular cell-secreted heparin-like compounds,...

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Bibliographic Details
Published in:Circulation research 1993-12, Vol.73 (6), p.1051-1060
Main Authors: Nugent, Matthew A, Karnovsky, Morris J, Edelman, Elazer R
Format: Article
Language:English
Subjects:
3T3 Cells
Animals
Biological and medical sciences
Blood Vessels - cytology
Blood Vessels - metabolism
Blood vessels and receptors
Cell Division - drug effects
Culture Media, Conditioned
Fibroblast Growth Factor 2 - antagonists & inhibitors
Fibroblast Growth Factor 2 - metabolism
Fibroblast Growth Factor 2 - pharmacology
Fundamental and applied biological sciences. Psychology
Heparin - pharmacology
Heparitin Sulfate - pharmacology
Heparitin Sulfate - physiology
Mice
Mitosis - physiology
Muscle, Smooth, Vascular - physiology
Vertebrates: cardiovascular system
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Summary:Basic fibroblast growth factor (bFGF) has been previously shown to be mitogenic for vascular smooth muscle cells (VSMCs) in vivo, but only after vascular injury. We show in the present study that the regulation of bFGF-stimulated VSMC proliferation, by vascular cell-secreted heparin-like compounds, correlates with inhibition of bFGF binding to cell-associated heparan sulfate proteoglycans. The stimulation of cultured VSMC proliferation by bFGF was markedly reduced when these cells were cocultured with confluent endothelial cells or confluent VSMCs (100.8±8.4% and 55.6±2.3% inhibition, respectively) or with conditioned media from these two cell types. Balb/c3T3 fibroblasts had no statistically significant effect on bFGF-stimulated VSMC proliferation. Vascular cell-conditioned media also inhibited bFGF binding to heparan sulfate proteoglycans on VSMCs, and the inhibition of binding correlated linearly with the inhibition of proliferation after a critical amount of binding was inhibited (44%) (r=.952, P
ISSN:0009-7330
1524-4571
DOI:10.1161/01.res.73.6.1051