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Heparin interactions with cultured human vascular endothelial and smooth muscle cells: Incidence on vascular smooth muscle cell proliferation

โœ Scribed by Jean-Marc Herbert; Jean-Pierre Maffrand


Publisher
John Wiley and Sons
Year
1989
Tongue
English
Weight
861 KB
Volume
138
Category
Article
ISSN
0021-9541

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โœฆ Synopsis


The binding, internalization, and metabolism of 13H]-heparin by human umbilical vein endothelial cells (HUVEC) and human umbilical arterial smooth muscle cells (HUASMC) have been characterized using 5ize-exclusion HPLC. Incubation of HUVEC with ['HI-heparin demonstrated selective binding of high-molecularweight (MW) components ( M W = 21 kd), which was followed by rapid, temperature-dependent internalization. Over the next 3 hours, this internalized I3H]-heparin was degraded to low-MW fragments (MW = 0.9 kd). Primary cultures of HUASMC selectively bound extremely high-MW components (MW = 40 kd) and also smaller components whose M W (0.9 kd) corresponded to that of the heparin metabolite(s) formed by HUVEC. Subcultured HUASMC bound only the 40-kd components. Internalization of heparin by smooth muscle cells (SMC) was significantly slower than that determined for HUVEC, and even after 4 hours there was no evidence of the heparin being metabolized. However, when incubating primary rabbit aortic SMC with purified low-MW heparin fragment(s) produced in culture by HUVEC, a significantly lower proliferative response of these cells (IC50 = 18.4 &ml) was obtained. Virtually no effect was observed with subcultured SMC in the range of the te5ted concentrations (0-20 kg/mI). These fragments were 10-to 1 !%fold more effective in inhibiting primary SMC growth than was standard heparin. Furthermore, heparin fractions in the same range of molecular weights, purified either after nitrous acid or heparinase depolynierization of standard heparin, showed no activity on primary SMC growth, thus indicating a high degree of selectivity of the heparin metabolite(s) produced by HUVEC in culture.


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