title: Down-regulation of lipoprotein lipase increases ABCA1-mediated cholesterol efflux in THP-1 macrophages.
abstract: The ATP-binding cassette transporter A1 (ABCA1) mediates the efflux of excess cholesterol from foam cells to lipid-poor apolipoprotein A-I, in a process called reverse cholesterol transport. Lipoprotein lipase (LPL) is a lipolytic enzyme expressed by macrophages within atherosclerotic lesions. Lentivirus-mediated RNA interference was used to genetically knock-down (KD) the expression of LPL in THP-1 macrophages. Silencing of the LPL gene was confirmed by end-point PCR, real time PCR, and protein analysis. Suppression of LPL expression correlated with a 1.6-fold up-regulation of ABCA1 mRNA levels, and resulted in a 4.5-fold increase in ABCA1-dependent cholesterol efflux. Replenishing LPL by addition of purified bovine LPL to the cell culture media resulted in down-regulation of ABCA1-mediated cholesterol efflux in both wild-type and LPL knockdown cells. These findings suggest an inverse correlation between macrophage LPL levels and ABCA1 cholesterol transport activity.
authors.affiliation: Department of Chemistry and Biochemistry, California State University Northridge, Northridge, CA 91330-8262, United States.
authors.forename: Ryoko L
authors.initials: RL
authors.lastname: Kawashima
authors.affiliation: Department of Chemistry and Biochemistry, California State University Northridge, Northridge, CA 91330-8262, United States. Electronic address: jheem.medh@csun.edu.
authors.forename: Jheem D
authors.initials: JD
authors.lastname: Medh
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism*; D001483:Base Sequence; D001692:Biological Transport; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D017931:DNA Primers; D006801:Humans; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D017931:DNA Primers; D002784:Cholesterol; D008071:Lipoprotein Lipase
keywords: ABCA1 transporter; Cholesterol efflux; Lipoprotein lipase; Reverse cholesterol transport; THP-1 macrophages; shRNA