Aortic glycosaminoglycans in atheroma and alloxan diabetes.

Abstract

(1) Rabbits and rats were fed a high-fat, high-cholesterol diet to produce lipid deposition in the wall of the aorta. The intima and inner media were examined for their content of lipids, protein-bound carbohydrates, and individual glycosaminoglycans. In addition, the rate of uptake of 35S from sulfate into the sulfated glycosaminoglycans was measured in some animals.(2) In the rat, lipid accumulation was minimal; there were increases in the protein-bound hexosamine and sialic acid and decreases in all the glycosaminoglycans (hyaluronic acid, heparan sulfate, chondroitin-4-sulfate, chondroitin-6-sulfate, and dermatan sulfate).(3) In the rabbit, lipid accumulation was marked in the normal appearing tissue and still greater in the "fatty streaks". There were associated increases in protein-bound hexosamine and hexose and, in the fatty streaks, of sialic acid also. The concentrations of all sulfated glycosaminoglycans were higher in the fatty streaks than in the surrounding tissue.(4) In the rat, the rate of synthesis of chondroitin sulfates, as reflected in sulfate-35S incorporation, was not increased, but the turnover of chondroitin sulfates as reflected in the fractional rate of 35S incorporation was increased; this is taken as evidence that the fall in concentration was due to an increase in the rate of removal. In the rabbit, both synthesis and turnover of chondroitin sulfates were greatly increased in the fatty streaks; the change in synthesis was greater and led to the increase in the concentrations of these substances.(5) The concentration of hyaluronic acid was increased in the aortae of alloxan diabetic animals. Sulfate incorporation was reduced, indicating decreased synthesis of sulfated glycosaminoglycans. Despite this, the aortae of diabetic animals had virtually the same composition (except for hyaluronic acid) as those of non-diabetics given the same diet.