The glycosaminoglycans of the human artery and their changes in atherosclerosis

Abstract

The levels of glycosaminoglycans (GAGs) of the intima and media of human arteries in atherosclerosis were determined by a recently introduced 2 dimensional electrophoresis technique which permits direct measurements of each of these macromolecules. To identify the arterial GAGs, they were fractionated by chromatography on a DEAE Sephadex A 25 column, and the resulting 3 fractions (hyaluronic acid [HA], heparan sulfate [HS], and the partially separated chondroitin sulfates B [CSB] and C [CSC]) were analyzed for their electrophoretic mobilities by this electrophoretic method, for their digestibility by highly specific hydrolases (leech hyaluronidase, heparinase, and chondroitinases ABC and AC) and for their iduronic acid content. From these studies, it is concluded that normal and atherosclerotic human aortas contain CSB, CSC, HA, and HS. Further, it could be demonstrated that CSB is a hybrid consisting of approximately 40% CSA and 60% CSB and that CSC appears to be a polymer consisting essentially of glucuronic acid and N acetylgalactosamine 6 sulfate. Classical CSA as well as chondroitin (CH) were not present in detectable amounts. In the relatively normal intima, the mean concentrations of the GAGs were found to be 4.7, 20.9, 1.3, and 5.1 mg/g of dry, defatted, decalcified tissue for CSB, CSC, HA, and HS, respectively. With the progression of atherosclerosis, there was a pronounced decrease in the total GAG content (from 32 to 18 mg) associated with a decrease in the CSC and HS levels but without a change in the HA concentration. Of particular interest, however, was the increase in the CSB level. In the media whose total GAG content averaged approximately 20 mg, no significant changes in these GAG levels were noted with the progression of the disease except for that of CSC. These findings may be important in explaining the increased lipoprotein and collagen deposition in the diseased aorta.