Proteoglycan composition of rabbit arterial wall under conditions of experimentally induced atherosclerosis

The concentration and composition of proteoglycans (PG) of the neointima developed following balloon catheter removal of aortic endothelium in rabbits, were assessed. PG were extracted from the aortic intimal-medial tissues with 4 M guanidinium chloride in the presence of protease inhibitors and purified subsequently by cesium chloride gradient ultracentrifugation and fractionation by high-performance liquid chromatography (HPLC). PG so obtained was analysed for its protein, cholesterol and glycosaminoglycan (GAG) content. For the characterization of the GAG moiety, an exhaustive proteolytic digestion was done. The GAG were then recovered by ethanolic precipitation and their relative distribution was determined after a selective enzymatic digestion using specific enzymes. Results show a significant increase in the amount of PG in the areas of the injured arterial wall covered by regenerated endothelium. In addition, changes in the composition of GAG were also found in the PG isolated from experimental animals when compared to PG isolated from normal aorta. A marked increase in the content of chondroitin sulfates and dermatan sulfate of injured tissue was seen. Hyaluronic acid content also changed in response to de-endothelialization and cholesterol feeding, but only moderately. The content of heparan sulfate remained unaffected in experimental tissues. Furthermore, cholesterol feeding aggravated the injury-induced increment of GAG. These findings are consistent with previously reported morphological observations, and correlate well with reports that arterial injury and cholesterol feeding act synergistically in the evolution of the atherosclerotic lesion and provide further evidence that the interaction of lipid and PG of the arterial wall may be of particular importance to our comprehension of the pathogenesis of atherosclerosis.