Experimentally induced metabolic acidosis in rabbits modulates the interaction of aortic glycosaminoglycan with plasma low-density lipoprotein—An interesting observation about the association of acidosis and atherosclerosis

Abstract

It is well established that arterial glycosaminoglycans (GAG) undergo compositional and structural modifications during the development of atherosclerosis. On the other hand, metabolic acidosis is a common feature of chronic renal patients known to present accelerated atherogenesis. The present study was performed to determine the influence of acidosis in the modifications of aortic GAG in a model of atherosclerosis in rabbits. For this purpose, four groups of rabbits were kept for 8 weeks on a regimen of normal, hypercholesterolemic, acidemic and hypercholesterolemic plus acidemic diets. No difference was detected in the total GAG concentration among animals fed with normal, hypercholesterolemic and acidemic diets. However, we observed an increase in total GAG content when acidosis was associated with hypercholesterolemia. This increase was more pronounced in the thoracic aortic segment. The interaction between LDL and the aortic GAG was evaluated by formation of insoluble complexes. The results showed that GAG extracted from hypercholesterolemic rabbits exhibited a lower ability to interact with LDL, when compared to those fed normal diet. On the other hand, GAG extracted from rabbits submitted to hypercholesterolemic plus acidemic diet, did not show this behavior. In addition, the molecular weight of GAG from hypercholesterolemic animals, is lower than those from animals fed normal diet. Surprisingly, acidosis associated with hypercholesterolemia did not exhibit this alteration, keeping the molecular weight close to the normal range. In view of these results, we hypothesize that acidosis itself does not affect either the GAG composition or its interaction with LDL, however in an atherogenic condition, as can be seen in renal failure individuals, it may alter the GAG concentration and the size of the glycan chains.