Altered dermatan sulfate structure and reduced heparin cofactor II-stimulating activity of biglycan and decorin from human atherosclerotic plaque

Biglycan and decorin are small dermatan sulfate-containing proteoglycans in the extracellular matrix of the artery wall, The dermatan sulfate chains a re known to stimulate thrombin inhibition by heparin cofactor II (HCII), a plasma proteinase inhibitor that has been detected within the artery wall. The purpose of this study was to analyze the HCII stimulatory activity of b iglycan and decorin isolated from normal human aorta and atherosclerotic le sions type II through VI and to correlate activity with dermatan sulfate ch ain composition and structure. Biglycan and decorin from plaque exhibited a 24-75% and 38-79% loss of activity, respectively, in thrombin-HCII inhibit ion assays relative to proteoglycan from normal aorta. A significant negati ve linear relationship was observed between lesion severity and HCII stimul atory activity (r = 0.79, biglycan; r = 0.63, decorin; p < 0.05), Biglycan, but not decorin, from atherosclerotic plaque contained significantly reduc ed amounts of iduronic acid and disulfated disaccharides Delta Di-2,4S and Delta Di-4,6S relative to proteoglycan from normal artery. Affinity coelect rophoresis analysis of a subset of samples demonstrated that increased inte raction of proteoglycan with HCII in agarose gels paralleled increased acti vity in thrombin-HCII inhibition assays. In conclusion, both biglycan and d ecorin from atherosclerotic plaque possessed reduced activity with HCII, bu t only biglycan demonstrated a correlation between activity and specific gl ycosaminoglycan structural features, Loss of the ability of biglycan and de corin in atherosclerotic lesions to regulate thrombin activity through HCII may be critical in the progression of the disease.