Experimental Atherosclerosis Section
Howard Kruth, MD, Principal Investigator
Our research program is directed
towards understanding the mechanisms by which cholesterol accumulates
within arteries causing atherosclerotic plaques to form, the cause
of most heart attacks and strokes. We are investigating endocytic
pathways by which endothelial cells transport LDL, cholesterol-carrying
lipoproteins, into the vessel wall, and by which macrophages within
the vessel wall then take up these LDL. Both processes contribute
to atherosclerotic plaque development. Biochemical, cell biological,
and molecular biological studies of LDL processing by these cells
in culture are being carried out. Our studies have led to the discovery
of a novel mechanism by which macrophages accumulate cholesterol
and transform into plaque-generating foam cells. Activated macrophages
take up LDL in the fluid-phase by receptor-independent pinocytosis
of LDL. Elucidation of the signaling pathways that mediate macrophage
pinocytosis of LDL will provide new drug targets with the potential
to limit plaque cholesterol accumulation.
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