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Heparin causes the accumulation of heparan sulfate in cultures of arterial smooth muscle cells.

Abstract：

:Heparin infusion in an experimental animal model of arterial injury causes a significant increase in the proteoglycan (PG) component of the extracellular matrix in the injured arteries (Snow, A. D., Bolender, R. P., Wight, T. N., and Clowes, A. W. (1990) Am. J. Pathol. 137, 313-330). The mechanisms responsible for this heparin-induced increase in arterial PGs are not understood. To address this question, we have examined the effect of heparin on PG synthesis and accumulation by aortic smooth muscle cells in culture. Heparin causes a dose-dependent increase in the accumulation of PGs while the greatest percentage change among the different types of PGs is a doubling of the amount of heparan sulfate (HS) accumulated in the cell layer. There is also a selective enrichment of HS in the trypsin-resistant component of the cell layer indicating a specific modification in intracellular PGs. This change is due to the accumulation of large HS glycosaminoglycans (GAGs) which elute at K(av) approximately 0.3 on Sepharose CL-6B (Mr approximately 50,000) under dissociative conditions and which are absent from the controls. These GAGs are located inside the cell as is indicated by their retention after heparitinase or trypsin treatment of the cell layer. Furthermore, the increased accumulation of labeled HS in steady-state heparin-treated cells above controls does not appear for several hours after the addition of [35S]sulfate, indicating that HS accumulation is due to decreased degradation of the HS and not new synthesis. This possibility is further supported by the fact that degradation of the intracellular large HS in trypsinized cells is delayed for 2 h by incubation with heparin. These results suggest that heparin may reduce the intracellular degradation of HS through competitive inhibition of endogenous heparitinase.

journal_name

Arch Biochem Biophys

journal_title

Archives of biochemistry and biophysics

authors

Potter-Perigo S,Wight TN

doi

10.1006/abbi.1996.0527

subject

Has Abstract

pub_date

1996-12-01 00:00:00

pages

19-26

issue

1

eissn

0003-9861

issn

1096-0384

pii

S0003-9861(96)90527-5

journal_volume

336

pub_type

杂志文章

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