Specificity of glycosaminoglycan suppression of endothelin-1 production by human umbilical vein endothelial cells

Abstract

Endothelin-1 (ET-1) is the most potent vasoconstrictor peptide found in nature. Its production is stimulated by thrombin. By inhibiting thrombin we have previously shown that heparin, a highly negatively-charged glycosaminoglycan (GAG), suppresses the production of ET-1 by cultured human umbilical vein endothelial cells (HUVEC). The purpose of our study is to determine the effect of other GAGs and related compounds on ET-1 production. The GAGs and related compounds used in the study were: chondroitin sulfate A, chondroitin sulfate B, chondroitin sulfate C, fucoidin, low molecular weight dextran sulfate, high molecular weight dextran sulfate, and hyaluronan. HUVEC were incubated for 48 hr with media containing these GAGs and related compounds and with media without GAG as control. ET-1 levels were measured by radioimmunoassay. GAGs and related molecules with higher sulfate content, heparin, chondroitin sulfate B, low and high molecular weight dextran sulfates significantly suppressed ET-1 production by HUVEC. Fucoidin also suppressed ET-1 production despite its lower sulfate content, probably because of its structural similarity to heparin. These compounds may be useful for future in vivo studies.