Phenotypic high-throughput screening in atherosclerosis research: focus on macrophages.
Atherosclerosis is a complex disease characterized by arterial lesions consisting of macrophage foam cells, smooth muscle cells, lymphocytes and other cell types. As atherosclerotic lesions mature, they can rupture and thereby trigger thrombosis that can result in tissue infarction. Macrophage foam cells develop in the subendothelial space when cells take up cholesterol from modified forms of low-density lipoprotein (LDL) and other apolipoprotein B-containing lipoproteins. Current therapies to limit atherosclerosis focus on altering the plasma lipid composition, most commonly by reducing circulating LDL levels. No current therapy is specifically designed to alter the cellular composition of atherosclerotic lesions. To address this deficit, phenotypic high-throughput drug screens have been developed to identify compounds that reduce the uptake of oxidized LDL by macrophages or to identify compounds that increase the efflux of cholesterol from macrophages. Additional phenotypic screens can be envisaged that address cellular processes in active atherosclerotic lesions including macrophage apoptosis and efferocytosis.
Muslin
Anthony J
AJ
Center for Cardiovascular Research, Washington University School of Medicine, 660 South Euclid Avenue, Box 8086, St. Louis, MO 63110, USA. amuslin@dom.wustl.edu
D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002784:Cholesterol / Q000378:metabolism*; D055808:Drug Discovery / Q000379:methods*; D005487:Foam Cells / Q000187:drug effects / Q000378:metabolism; D057166:High-Throughput Screening Assays; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D058990:Molecular Targeted Therapy; D010641:Phenotype; D057170:Translational Research, Biomedical
D000960:Hypolipidemic Agents; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D002784:Cholesterol