Enhanced ability of heparin-carrying polystyrene (HCPS) to bind to heparin-binding growth factors and to inhibit growth factor-induced endothelial cell growth.
Heparin-carrying polystyrene (HCPS) consists of low-molecular-weight heparin chains enriched in trisulfated disaccharide structures linked to a polystyrene core. In this study, the interactions between HCPSs of various molecular weights and heparin-binding growth factors, VEGF(165), FGF-2, and HGF, were compared to the interactions of the same factors with native heparin, periodate-oxidized heparin (IO(4)-heparin) and periodate-oxidized alkaline-degraded heparin (IO(4)-LMW-heparin). The binding of each growth factor to heparin-agarose beads (heparin-beads) was more strongly inhibited by HCPSs in a molecular weight-dependent manner than by native heparin or the modified heparins, indicating a stronger interaction between HCPS and these growth factors. HCPSs also inhibit heparin-binding growth factor-induced endothelial cell growth in a molecular weight-dependent manner much more strongly than the native or modified heparins. However, HCPSs did not inhibit the mitogenic activity of VEGF(121), which has a non-heparin-binding nature. Thus, HCPSs exhibit enhanced abilities to interact with each of the heparin-binding growth factors studied and to inhibit heparin-binding growth factor-induced endothelial cell proliferation in a molecular weight-dependent manner. These effects might be ascribed to the heparin-clustering effect of HCPSs.
Ishihara
M
M
Division of Biomedical Engineering, National Defense Medical College, Namiki, Tokorozawa, Saitama 359-8513, Japan.
Ono
K
K
Ishikawa
K
K
Hattori
H
H
Saito
Y
Y
Yura
H
H
Akaike
T
T
Ozeki
Y
Y
Tanaka
S
S
Mochizuki
H
H
Kurita
A
A
D003331:Coronary Vessels / Q000166:cytology; D004187:Disaccharides / Q000032:analysis; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology*; D016228:Endothelial Growth Factors / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006001:Glycoconjugates / Q000737:chemistry / Q000494:pharmacology; D006131:Growth Inhibitors / Q000494:pharmacology; D006133:Growth Substances / Q000378:metabolism*; D006493:Heparin / Q000737:chemistry / Q000494:pharmacology*; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D008222:Lymphokines / Q000378:metabolism; D011137:Polystyrenes / Q000737:chemistry / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D004187:Disaccharides; D004337:Drug Carriers; D016228:Endothelial Growth Factors; D006001:Glycoconjugates; D006131:Growth Inhibitors; D006133:Growth Substances; D008222:Lymphokines; D011137:Polystyrenes; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D017228:Hepatocyte Growth Factor; D006493:Heparin