Polydispersity of acidic glycosaminoglycan components in human liver and the changes at different stages in liver cirrhosis

Abstract

The aim of this study was to characterize acidic glycosaminoglycan components in normal human liver and in alcoholic cirrhosis, and to determine whether the proportions of individual glycosaminoglycans change with advancing cirrhosis. Acidic glycosaminoglycans are components of extracellular matrices and consist of repeating disaccharides of hexosamine and hexuronic acid with molecular weights ranging from 5 X 10(3) to 5 X 10(4), except for hyaluronic acid, whose molecular weight ranges from 3 X 10(4) to 1.6 X 10(6). The acidic glycosaminoglycan components in normal liver and at different stages of liver cirrhosis were found to be polydisperse as to the molecular weight and the degree of sulfation. The increased content of glycosaminoglycans with advancing liver cirrhosis was related to those of heparan sulfate and dermatan sulfate components. Heparan sulfates were the most prominent components of smaller molecular weight fractions. In the normal state, moderate amounts of dermatan sulfate and the oversulfated isomer were present in intermediate molecular weight fractions, but increasing amounts of the components shifted to higher molecular weight fractions with advancing cirrhosis. A small amount of hyaluronic acid was found in higher molecular weight fractions and the amount increased at the initial stage as a reversible phenomenon. The possible roles of hepatic glycosaminoglycan components in the process of fibrosis are discussed.