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Leukocyte adhesion molecules in atherogenesis
M I Cybulsky1, A H Lichtman, L Hajra
1Department of Laboratory Medicine and Pathobiology, University of Toronto, The Toronto General Hospital Research Institute, ON, Canada. myron.cybulsky@utoronto.ca
Abstract:
Functions of mononuclear leukocytes and endothelial cell leukocyte adhesion molecules in the formation of early atherosclerotic lesions is discussed. The main transgenic mouse models developed to study cholesterol metabolism and atherosclerotic lesion formation, including apolipoprotein E knockout and low density lipoprotein receptor knockout (LDLR-/-) mice, are reviewed. Differences in their dependence on dietary cholesterol supplementation is emphasized and a new semi-purified, cholate-free mouse diet for LDLR-/- mice is described. This diet is highly reproducible, versatile (pellet, powder or liquid formulations), inexpensive and promotes hypercholesterolemia and atherosclerotic lesion development despite absence of sodium cholate. We describe the expression patterns of leukocyte adhesion molecules in rabbit and mouse models of atherosclerosis and compare them to humans. Finally, ongoing studies are summarized which utilize transgenic mice to assess the roles of individual adhesion molecules in atherosclerotic lesion formation.