Arterial glycosaminoglycans are considered to be important in atherogenesis due to their ability to trap lipid inside the vessel wall and to influence cellular migration and proliferation. Atherosclerotic lesions have displayed an altered glycosaminoglycan content and distribution. Diabetes is a recognized risk factor for atherosclerosis, but no information is available on the arterial glycosaminoglycans in human diabetes. We examined glycosaminoglycans in normal and atherosclerotic intima of non-diabetic and Type 2 (non-insulin-dependent) diabetic patients. Intima was stripped from autopsy samples of thoracic aortas; normal and plaque areas were separated. Glycosaminoglycans were isolated by delipidation, proteolytic digestion, and precipitation and characterized by quantitation of total glycosaminoglycan and evaluation of glycosaminoglycan distribution by electrophoresis and densitometry. Results indicate a significant decrease in total glycosaminoglycan and significant changes in their distribution in atherosclerotic plaques: a relative decrease in heparan sulphate, a relative increase in dermatan sulphate and thus a decrease in the ratio of heparan sulphate to dermatan sulphate. A similar but less marked change in the ratio was found in normal intima of diabetic subjects, while in their plaques this change was more pronounced. This suggests that changes in arterial glycosaminoglycans (especially the ratio of heparan sulphate to dermatan sulphate) precede the development of lesions in diabetes and may be important in atherogenesis.

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We studied proteoglycan distribution In areas of spontaneously occurring high and low permeability by TEM examination of ruthenium red-stained sections of the aortic arch of normollpemlc and hyperllpemlc pigs. We noted granules of two sizes: those smaller than 20 nm contained heparan sulphate, and those from 20 to 50 nm In size contained chondroltln or dermatan sulphate. In the aortas of pigs fed a normal diet, there were significantly more granules of both types In low permeability areas than in areas permeable to Evans blue dye. This is consistent with the theory that glycosamlnoglycan provides a component for the control of aortic permeability. 4 It has been shown that permeable areas accumulate more cholesterol than contiguous, less permeable areas, when the animal studied has been fed a hypercholesterolemic diet.5 Such areas have generally been considered the sites where the initial stages of the atherosclerotic process develop. 6In lipid-fed animals, early atherogenic changes have been described in anatomical locations similar to those that are permeable to Evans blue in macroscopically normal vessels.16 " 8 More recently Gerrity et al. 9 have shown that, in the prelesion stages in swine fed an atherogenic diet, more monocytes accumulate on the endothelial surface of the areas per- meable to Evans blue dye than on the impermeable areas, and that lipid-filled monocytes were present in the intima of blue areas but not in the white areas. Subsequently, raised fatty lesions developed in the arch within the confines of the Evans blue dye uptake.10

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