A Proposed Structure of Chondroitin 6‐Sulfate Proteoglycan of Human Normal and Adjacent Atherosclerotic Plaque

Chondroitin sulfate proteoglycan monomers were prepared from lntima media minces of grossly normal human aorta and adjacent fatty fibrous atherosclerotic plaques. Glycosaminoglycan chains prepared from monomer from normal aorta displayed a normal distribution profile on Ultrogel ACA 54 with a kav of 0.48, whereas those of atherosclerotic aorta displayed a bimodal distribution (major peak, K2 0.35; minor peak, kav 0.70). The Mr of glycosaminoglycans from normal aorta was estimated to be 1.5 × 104. For atherosclerotic aorta, the majority of chains were 2.0 × lo4 while the smaller population was 1.2 × lo4. All glycosaminoglycans were identified as chondroitin sulfate sulfated at the C-6 position. The amino acid compositions of both core proteins were similar with M, of about 1.6 × lo5. After β-ellmination In the presence of sodium borohydride prior to acid hydrolysis, chondroitin sulfate proteoglycan from normal aorta had reductions in serine from 109 to 68 and in threonine from 11 7 to 55. For the monomer from atherosclerotic plaque, reductions in serine and theonine, respectively, were from 103 to 81 and from 107 to 77 residues per 1000. The results suggested fewer chondroitin sulfate chains and oligosaccharides on the core protein in the proteoglycan of atherosclerotic plaque. Compared to normal aorta, substituted serines and threonines in the proteoglycan of atherosclerotic plaque were about half, respectively, 38% vs 21 %for serine, 53% vs 28% for threonine. It is estimated that in atherosclerotic plaque there are fewer, but longer, chondroitin sulfate chains per core protein, translating into a smaller overall monomer size in atherosclerotic plaque.