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

Endothelin-1 (ET-1) is the most potent vasoconstrictor peptide found in nat ure. Its production is stimulated by thrombin. By inhibiting thrombin we ha ve previously shown that heparin, a highly negatively-charged glycosaminogl ycan (GAG), suppresses the production of ET-1 by cultured human umbilical v ein 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 an d related compounds used in the study were: chondroitin sulfate A, chondroi tin sulfate B, chondroitin sulfate C, fucoidin, low molecular weight dextra n sulfate, high molecular weight dextran sulfate, and hyaluronan. HUVEC wer e incubated for 48 hr with media containing these GAGs and related compound s and with media without GAG as control. ET-1 levels were measured by radio immunoassay. GAGs and related molecules with higher sulfate content, hepari n, chondroitin sulfate B, low and high molecular weight dextran sulfates si gnificantly suppressed ET-1 production by HUVEC. Fucoidin also suppressed E T-1 production despite its lower sulfate content, probably because of its s tructural similarity to heparin. These compounds may be useful for future i n vivo studies.