Trends in Glycoscience and Glycotechnology
Online ISSN : 1883-2113
Print ISSN : 0915-7352
ISSN-L : 0915-7352
Control of Cardiovascular Biology through the Synthesis of Heparan Sulfate Proteoglycans Bearing Specific GAG Structures
Nicholas W. ShworakRobert D. Rosenberg[in Japanese]
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1998 Volume 10 Issue 52 Pages 175-192

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Abstract

We review the role of HSPGs in mediating the actions of three critical effectors of the cardiovascular system-the fibroblast growth factors (FGFs), lipoprotein lipase and antithrombin (AT). HSPGs modulate the transduction of signals by FGFs through FGF receptors, serve to transport and localize lipoprotein lipase to key sites of action, and directly stimulate the anticoagulant activity of AT. These diverse mechanisms of action are all made possible by highly specific interactions between each effector molecule and distinct sequences of monosaccharides of the HS chain. These sequences are predominantly determined by the nonrandom arrangement of N-, 2-O-, 6-O-, and 3-O-sulfate groups along the heparan sulfate chain (HS); thus, the biologic functions of HSPGs are controlled by biosynthetic events which define HS fine structure. In particular, endothelial cell production of the AT binding site is regulated by the kinetically limiting activity of 3-O-sulfotrans-ferase-1. A comparison of the structural and functional properties of the known HS sulfotransferases reveals that multiple isoforms, with clear cut precursor/product relationships, can occur and function within an at least partially ordered biochemical pathway. On the basis of these observations, we propose a model for the regulated synthesis of defined HS sequences.

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