Acidic glycosaminoglycans in human atherosclerotic cerebral arterial tissues

The glycosaminoglycan (GAG) content of normal and atherosclerotic areas of cerebral arterial tissue isolated from human males was measured. The main trunk and distal branches of the arteries were obtained at autopsy on 12-89-year-old Japanese subjects. The GAG components were analysed by high-performance liquid chromatography (HPLC) after enzymatic digestion, using specific GAG lyases. Both total GAGs and water content were lower in the diseased arteries than those in the normal state. In contrast, the reverse was noted for the lipid content. The main GAG component of the normal cerebral arteries was heparan sulfates (HS), comprising half the total GAGs, followed by dermatan sulfate (DS) and chondroitin 6-sulfate (Ch-6S) constituting 1/5 to 1/9 the total GAGs. Chondroitin 4-sulfate (Ch-4S) comprised approx. 1/10 the total GAGs. Oversulfated chondroitin sulfate isomers were detected as novel peaks of the chondroitin sulfate types G, B, E and H on HPLC analysis. Small amounts of hyaluronic acid (HA) and chondroitin were also detected. The total GAG content decreased with severity of atherosclerosis. The content and proportions of HS to the total GAGs decreased remarkably, and those of Ch-4S, HA and chondroitin showed a moderate decrease. The reverse was the case for those of DS, Ch-6S and oversulfated DS and/or Ch-S. The lipid components, in particular cholesterol ester, in the diseased tissue were significantly greater than in the visibly normal parts while the opposite was the case for the water content. Thus, the GAG species and their contents in human cerebral arteries showed a characteristic distribution. As oversulfated DS and Ch-S isomers have anticoagulant and anti-atherosclerotic activities, they may play a pertinent role in the disease process.