Summary
Derivatized dextrans exert a stimulatory effect on the in vitro growth of human umbilical vein endothelial cells (HUVEC). Measurements of growth were monitored by [3H]thymidine uptake and cell numbers. Our results show that some derivatized dextrans at 4 µg/ml (88 nM) increase the [3H]thymidine incorporation, whereas starting dextran (40 000 Da), dextran sulfate, and carboxymethyl dextran have no effect. In addition, heparin under similar experimental conditions shows a slight inhibitory effect on the HUVEC growth. The stimulatory effect of derivatized dextrans was also found when HUVEC grew during 7 days in medium containing 2% fetal bovine serum. We also observed that derivatized dextrans had no effect on the mitogenic activity of acidic fibroblast growth factor, a mitogenic factor for several cell types including HUVEC. By assessment of [3H]thymidine uptake at 48 h without serum, we concluded that the exogenous growth factors were not involved in the proliferative activity of these components. The stimulatory effects are related to the chemical nature and the proportion of substituents on the synthetic polysaccharides. The data indicate that benzylamide sulfonated groups play a key role in the stimulation of HUVEC growth. Neither carboxyl nor sulfate groups alone exhibit this effect. Thus, the stimulatory capacity of dextran derivatives depends strongly on the respective ratios of the functional groups.
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Avramoglou, T.; Jozefonvicz, J. Derivatized dextrans inhibition of smooth muscle cells proliferation in culture. J. Biomat. Sci. Polymer Edn. 3:149–154; 1991.
Barzu, T.; Molho, P.; Tobelem, G., et al. Binding and endocytosis of heparin by human endothelial cells in culture. Biochem. Biophys. Acta 845:196–203; 1985.
Barzu, T.; Van Rijn, J. L. M. L.; Petitou, M., et al. Endothelial binding sites for heparin. Biochem. J. 238:1085–1097; 1986.
Barzu, T.; Lormeau, J. C.; Petitou, M., et al. Heparin derived oligosaccharide: affinity for acidic fibroblast growth factor and its growth-promoting activity for human endothelial cells. J. Cell. Physiol. 140:538–548; 1989.
Castellot, J. J.; Addonizio, M. L.; Rosenberg, R. D., et al. Cultured endothelial cells produce a heparin-like inhibitor of smooth muscle cell growth. J. Cell Biol. 90:372–379; 1981.
Castellot, J. J.; Beeler, D. L.; Rosenberg, R. D., et al. Structural determinants of the capacity of heparin to inhibit the proliferation of vascular smooth muscle cells. J. Cell. Physiol. 120:315–320; 1984.
Castellot, J. J.; Wong, K.; Herman, B., et al. Binding and internalization of heparin by vascular smooth muscle cells. J. Cell. Physiol. 124:13–20; 1985.
Castellot, J. J.; Choay, J.; Lormeau, J. C., et al. Structural determinants of the capacity of heparin to inhibit the proliferation of vascular smooth muscle cells. II. Evidence for a pentasaccharide sequence that contains a 3-O-sulfate group. J. Cell Biol. 102:1979–1984; 1986.
Castellot, J. J. Heparan sulfates: physiologic regulators of smooth muscle cell proliferation? Am. J. Respir. Cell. Mol. Biol. 2:11–12; 1990.
Cook, P. W.; Mattox, P. A.; Keeble, W. W., et al. Inhibition of autonomous human keratinocyte proliferation and amphiregulin mitogenic activity by sulfated polysaccharides. In Vitro Cell. Dev. Biol. 28A:218–222; 1992.
Courty, J.; Loret, C.; Chevallier, B., et al. Biochemical and comparative studies between eye- and brain-derived growth factor. Biochimie 69:511–517; 1987.
Crepon, B.; Maillet, F.; Kazatchkine, M. D., et al. Molecular weight dependency of the acquired anticomplementary and anticoagulant activities of specifically substituted dextrans. Biomaterials 8:248–253; 1987.
Edelman, E. R.; Adams, D. H.; Karnovsky, M. J. Effect of controlled adventitial heparin delivery on smooth muscle cell proliferation following endothelial injury. Proc. Natl. Acad. Sci. USA 87:3773–3777; 1990.
Fritze, L. M. S.; Reilly, C. F.; Rosenberg, R. D. An antiproliferative heparan sulfate species produced by postconfluent SMC. J. Cell Biol. 100:1041–1049; 1985.
Gospodarowicz, D.; Cheng, J. Heparin protects basic and acidic FGF from inactivation. J. Cell. Physiol. 128:475–484; 1986.
Jaffe, E. A.; Nachman, R. L.; Becker, C. G., et al. Culture of human endothelial cells derived from umbilical veins. J. Clin. Invest. 52:2745–2756; 1973.
Lane, D. A.; Lindahl, U. Heparin. In: Lane, D. A.; Lindahl, U., eds. Chemical and biological properties, clinical applications. London: Edward Arnold; 1989.
Logeard, D.; Avramoglou, T.; Letourneur, D., et al. Capacity of heparin and derivatized dextrans to inhibit vascular smooth muscle cell proliferation. American Society for Cell Biology, Abstract 1611 (A174), Dec. 8–12; 1991.
Mauzac, M.; Jozefonvicz, J. Anticoagulant activity of dextran derivatives. Part I: Synthesis and characterization. Biomaterials 5:301–304; 1984.
Mauzac, M.; Maillet, F.; Jozefonvicz, J., et al. Anticomplementary activity of dextran derivatives. Biomaterials 6:61–63; 1985.
Resink, T. R.; Scott-Burden, T.; Baur, U., et al. Decreased susceptibility of cultured smooth muscle cells from SHR rats to growth inhibition by heparin. J. Cell. Physiol. 138:137–144; 1989.
Rosenbaum, J.; Tobelem, G.; Molho, P., et al. Modulation of endothelial cell growth induced by heparin. Cell Biol. Int. Rep. 10:437–446; 1986.
Sorimachi, K.; Watanabe, K.; Yamazaki, S., et al. Inhibition of fibroblast growth by polyanions; effects of dextran sulfate and liginin derivatives. Cell Biol. Inter. Rep. 16(1):63–71; 1992.
San Antonio, J. D.; Lander, A. D.; Wright, T. C., et al. Heparin inhibits the attachment and growth of Balb/c-3T3 fibroblasts on collagen substrata. J. Cell. Physiol. 150:8–16; 1992.
Tardieu, M.; Slaoui, F.; Jozefonvicz, J., et al. Biological and binding studies of acidic fibroblast growth factor in the presence of substituted dextran. J. Biomat. Sci. Polymer Edn. 1:63–70; 1989.
Tardieu, M.; Gamby, C.; Avramoglou, T., et al. Derivatized dextrans mimic heparin as stabilizers, potentiators, and protectors of acidic or basic FGF. J. Cell. Physiol.; 150:194–203; 1992.
Vaudaux, P.; Avramoglou, T.; Letourneur, D., et al. Inhibition by derivatized dextrans ofStaphylococcus aureus adhesion to fibronectincoated biomaterials. In: Advances in biomaterials, Amsterdam: Elsevier; in press; 1992.
Vischer, P.; Buddecke, E. Different action of heparin and fucoidan on arterial smooth muscle cell proliferation and thrombospondin and fibronectin metabolism. Eur. J. Cell Biol. 56:407–414; 1991.
Wright, T. C.; Johnston, T. V.; Castellot, J. J., et al. Inhibition of rat cervical epithelial cell growth by heparin and its reversal by EGF. J. Cell. Physiol. 125:499–506; 1985.
Wright, T. C.; Pukac, L. A.; Castellot, J. J., et al. Heparin suppresses the induction of c-fos and c-myc mRNA in murine fibroblasts by selective inhibition of a protein kinase C-dependent pathway. Proc. Natl. Acad. Sci. USA 86:3199–3203; 1989.
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Letourneur, D., Champion, J., Slaoui, F. et al. In vitro stimulation of human endothelial cells by derivatized dextrans. In Vitro Cell Dev Biol - Animal 29, 67–72 (1993). https://doi.org/10.1007/BF02634373
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DOI: https://doi.org/10.1007/BF02634373