Keiji Nakagami

Monoclonal antibodies recognizing lipid-laden cells and extracellular regions with lipid-deposits in atherosclerotic aorta.

Monoclonal antibodies against lipid-laden cells and against extracellular regions of lipid-deposits in atherosclerotic aorta were prepared. Mice were immunized with a delipidated homogenate of atherosclerotic aorta of Watanabe-heritable hyperlipidemic rabbits. Hybridomas were obtained by fusion and cultured in hypoxanthine, aminopterin and thymidine selection medium. Specific antibodies were selected by indirect immunohistochemical staining of frozen sections of atherosclerotic aorta. Nine clones that produced antibodies that stained the atherosclerotic intima exclusively were selected and cloned by limiting dilution. Finally two clones (FCR1a/201F, FCR1b/ 904B) producing antibodies specific to lipid-laden cells and one clone (EMR1a/212D) producing an antibody specific to regions with lipid deposits in the extracellular matrix were established. These monoclonal antibodies may help in understanding how lipids accumulate in atherosclerosis.

Endothelial Injury and Accumulation of Cholesterol Ester Derived from Circulating Lipoproteins

To elucidate the mechanism how lipoproteins transport through the endothelial barrier, an in vitro model of transcellular transport of macromolecules was developed.