AGE-DEPENDENT MODULATION OF HEPARAN-SULFATE STRUCTURE AND FUNCTION

Heparan sulfate interacts with growth factors, matrix components, effe cters and modulators of enzymatic catalysis as well as with microbial proteins via sulfated oligosaccharide domains. Although a number of su ch domains have been characterized, little is known about the regulati on of their formation in vivo. Here we show that the structure of huma n aorta heparan sulfate is gradually modulated during aging in a manne r that gives rise to markedly enhanced binding to isoforms of platelet -derived growth factor A and B chains containing polybasic cell retent ion sequences. By contrast, the binding to fibroblast growth factor 2 is affected to a much lesser extent. The enhanced binding of aorta hep aran sulfate to platelet-derived growth factor is suggested to be due to an age-dependent increase of GlcN 6-O-sulfation, resulting in incre ased abundance of the trisulfated L-iduronic acid (2-OSO3)-GlcNSO(3)(6 -OSO3) disaccharide unit. Such units have been shown to hallmark the p latelet-derived growth factor A chain-binding site in heparan sulfate.