Co-localization of aortic apolipoprotein B and chondroitin sulfate in an injury model of atherosclerosis

Abstract

In vitro, chondroitin sulfate (CS) proteoglycans (PGs) bind with high-affinity lipoproteins (LPs) containing apolipoprotein B (apo B), and cultured monocytes incubated with LP-PG complexes transform into foam cells (FCs). Consequently, arterial PGs are thought to contribute to the accumulation of LPs in atherosclerotic lesions, but their in vivo interaction has yet to be demonstrated. Balloon catheterization of rabbit aorta modifies the normal aortic distribution of endogenous LPs containing apo B, and determines their accumulation in normocholesterolemic conditions. The distribution of aortic CS-PGs parallels that of apoB within the neointima of injured aortas and might contribute to a favorable environment for LP sequestration within the lesions. To visualize the in situ relationship between apo B and CS-PG, we performed experiments for double detection by immunofluorescence and by post-embedding electron microscope immunogold. The results indicated that the colocalization of endogenous LPs containing apo B and of the large intimal CS-PGs in advanced lesions developed under the regenerated endothelium. At the ultrastructural level, frequent associations were visualized in the extracellular space and in relation to FCs. The close spatial relation between CS-PG and apo B inside the aortic lesions seems to support the hypothesis of their in situ interaction and of a simultaneous cellular uptake, and may be related to the development of both extracellular lipid deposits and the formation of FCs in atherogenesis.