Effect of Cholesterol Feeding and Pantethine Treatment on Complexes between Lipids a Arterial Connective Tissue Macromolecules in Specific Pathogen-Free Rabbits

Abstract

SummaryThe present study was designed to clarify the significance of complex formation of lipoproteins with extracellular connective tissue macromolecules during lipid accumulation in the arterial wall in SPF rabbits fed on a 0.5% cholesterol diet for six weeks. The effect of pantethine, a new hypolipidemic drug, on their complex formation and lipid accumulation was also studied. The levels of cholesterol bound to glycosaminoglycan, collagen and elastin in the aortic tissues were significantly increased in the atherogenic-diet group. The present results suggest the importance of complex formation of lipoproteins with elastin for lipid accumulation in atherosclerotic lesions. From the results on the ratios of oleic acid/linoleic acid in cholesteryl esters in the plasma and aortic elastin fractions, the cholesteryl esters accumulated on the connective tissue macromolecules in the atherosclerotic rabbits might be derived from the plasma directly, in addition to vascular cell-derived cholesteryl esters. Treatment with pantethine significantly reduced the increased levels of cholesterol in the plasma and the aortic tissues of the cholesterol-fed rabbits. The results suggest that pantethine acts directly on the arterial tissues, in addition to its hypolipidemic effect. These biochemical results were confirmed by the histological findings.