Abstract 1657: Binding and Uptake of Oxysterols by Vascular Smooth Muscle Cells through the Cluster of Differentiation (CD)-1d Protein
Background– The MHC-class I-like molecule, CD1d, might play a role in lipid antigen presentation implicated in atherogenesis due to its hydrophobic binding pockets. Interestingly, CD1d is expressed on SMCs in lipid-rich atherosclerotic plaques. Since the phenomenon of SMC foam cell formation is poorly understood, we hypothesize the CD1d mediates the binding and internalization of oxidized cholesterol by SMCs in atherosclerosis leading to SMC foam cell formation.
Methods and Results– Stable cell lines (SMC) overexpressing CD1d were selected and used for binding and uptake studies. The oxysterol 3H-7-ketocholesterol (7K) was used to assay the binding and uptake capability of the transfected cells via β-counting. Cold 7K and 25-hydroxycholesterol (25OH) were examined as potential CD1d lipid ligands found in atherosclerotic plaques. Competitors (αGC, anti-CD1d antibody (Ab), cholesterol, anti-CD36 Ab, and non-immune IgG) were used to test the specificity of CD1d binding and uptake in the transfected cells. CD1d transfected cells were able to bind and uptake more 3H-7K than mock transfected cells. 3H-7K binding was inhibited by the addition of cold 7K and 25OH, αGC, and anti-CD1d Ab (Fig 1⇓). However, cholesterol, anti-CD36 Ab, and non-immune IgG failed to compete 3H-7K binding in the transfected cells.
Conclusions– CD1d overexpression significantly increased the binding and uptake of oxysterols, 7K and 25OH, potentiating its role in SMC-derived foam cell formation in lipid-rich atherosclerotic plaques. CD1d may therefore act as a scavenger receptor-like protein participating in the metabolism of chemically modified lipids or lipoproteins in atherosclerosis.