Journal of Clinical & Experimental Pharmacology

Abstract

Aortic Smooth Muscle Cells from ApoE^(-/-) Mice Secrete Biglycan with Hyperelongated Glycosaminoglycan Chains

Narin Osman, Robel Getachew and Peter J Little

Atherosclerosis is the major underlying process of cardiovascular disease. Atherosclerosis commences with an initial pre-inflammatory phase of the trapping and accumulation of lipids in the vessel wall and this is followed by an inflammatory response. The trapping of lipids occurs via binding to proteoglycans, specifically biglycan, with hyperelongated glycosaminoglycan (GAG) chains. Models have been developed to study the aetiology as well as the effectiveness of medical and experimental interventions in preventing atherosclerosis. ApoE is an apolipoprotein associated with removal of lipids from peripheral tissues. Disruption of the ApoE gene in C57BL/6 mice produces mice which are ApoE-/- (ApoE deficient) and show elevated plasma lipids and accelerated development of atherosclerosis which is exacerbated on a high fat diet. These mice are widely used in studies of atherosclerosis. We investigated the possibility that changes in the size of biglycan might participate in the development of atherosclerosis in ApoE-/- mice. We prepared Aortic Smooth Muscle Cell (ASMC) cultures by the digestion technique from ApoE-/- and ApoE+/+ mice and studied the size of biglycan secreted by both cell types. The biglycan secreted by ASMCs for ApoE-/- mice was larger than that from ApoE+/+ ASMCs. The difference was not eliminated by treatment of cells with a high concentration of Platelet Derived Growth Factor (PDGF) or by treatment with the PDGF antagonist, imatinib. The size difference was however observed in the small free GAG chains (xyloside GAGs) secreted in cells supplemented with exogenous xyloside as a cellular assay of GAG synthesizing capacity. This result suggests that there is a hyperactivity of the fundamental GAG synthesizing capacity in the ASMCs from ApoE-/- mice. These data suggest that hyperelongated biglycan might be contributing to lipid accumulation in ApoE-/- mice used in studies of atherosclerosis and that some of the medical interventions might have an action to reverse this hyperelongation response.