Disaccharide Composition of Glycosaminoglycan Chains in Growing Vascular Endothelial Cells in Culture after Exposure to Lead

Abstract

Heparan sulfate (HS) chains bind and activate fibroblast growth factor-2 (FGF-2) depending on their microstructure. The glycosaminoglycan chains present particularly as a large HS proteoglycan perlecan in vascular endothelial cells. A heavy metal lead induces a lower response to FGF-2 by inhibition of perlecan synthesis and inhibits the proliferation of the cells. The present study was undertaken to address the question whether lead influences the formation of HS chains in vascular endothelial cells. The data indicate that lead decreases the amount of disaccharide units including hexuronic acid-N-acetylglucosamine, hexuronic acid-N-sulfated glucosamine and 2-O-sulfated hexuronic acid-N-sulfated glucosamine in HS chains accumulated in the cell layer and the conditioned medium. However, no percentage of any disaccharide unit was affected by the metal. The percentage of disaccharide units in chondroitin/dermatan sulfate was also unaffected by lead. The present data support the hypothesis that lead-induced lower response of vascular endothelial cells to endogenous FGF-2 mainly results from a decrease in perlecan molecules of extracellular matrix as a result of selective inhibition of perlecan core protein synthesis rather than a change in the HS structure.