Effect of endothelium on glycosaminoglycan accumulation in injured rabbit aorta.
Academic Article
Overview
abstract
Previous studies have indicated that reendothelialized regions of injured rabbit aortas are more susceptible to diet-induced atherosclerosis than persistently deendothelialized regions or uninjured aortas. However, the mechanism responsible for this selective lipid deposition is not understood. One possibility is that these regions differ with respect to the quantity and type of glycosaminoglycan-containing proteoglycans which are known to interact with lipoproteins. To determine whether these regions differed with respect to their glycosaminoglycan composition, the authors divided 53 rabbits into four groups. Groups IA and IB were fed a regular diet beginning 5 weeks prior to aortic deendothelialization; Groups IIA and IIB were fed the same diet supplemented with 0.5% cholesterol. The rabbits were continued on these diets following aortic deendothelialization with a balloon catheter. Those in Groups IA and IIA were sacrificed either at 2-5 weeks or 6-8 weeks following deendothelialization; proteoglycans were assessed morphometrically following staining with alcian blue. Groups IB and IIB were sacrificed at 10 weeks following injury; glycosaminoglycans were extracted from deendothelialized and reendothelialized aortas, separated by electrophoresis, and quantitated by scanning densitometry. Morphometric analysis of stained aortic sections revealed significantly increased quantities of alcianophilic material in the neointima of reendothelialized aortas as compared with deendothelialized aortas in both diet groups. Chemical analysis revealed significantly more of each glycosaminoglycan in reendothelialized aortas when compared with deendothelialized or uninjured aortas. The major glycosaminoglycans present in all regions were heparan sulfate and chondroitin sulfate; and although absolute quantities of these particular glycosaminoglycans increased in the reendothelialized region, their relative percentages remained the same for each area analyzed. Cholesterol feeding did not appear to influence glycosaminoglycan concentration and composition in reendothelialized and deendothelialized regions when compared with normal diets, but cholesterol feeding alone did increase aortic glycosaminoglycans in uninjured aortas. The results suggest that the presence of endothelium influences the quantity and type of glycosaminoglycans accumulating in the neointima, and that the differences in proteoglycans in the reendothelialized artery may account at least in part for the propensity of this area to accumulate lipid and evolve as atherosclerosis.
