title: The GPIHBP1-LPL complex is responsible for the margination of triglyceride-rich lipoproteins in capillaries.
abstract: Triglyceride-rich lipoproteins (TRLs) undergo lipolysis by lipoprotein lipase (LPL), an enzyme that is transported to the capillary lumen by an endothelial cell protein, GPIHBP1. For LPL-mediated lipolysis to occur, TRLs must bind to the lumen of capillaries. This process is often assumed to involve heparan sulfate proteoglycans (HSPGs), but we suspected that TRL margination might instead require GPIHBP1. Indeed, TRLs marginate along the heart capillaries of wild-type but not Gpihbp1⁻/⁻ mice, as judged by fluorescence microscopy, quantitative assays with infrared-dye-labeled lipoproteins, and EM tomography. Both cell-culture and in vivo studies showed that TRL margination depends on LPL bound to GPIHBP1. Notably, the expression of LPL by endothelial cells in Gpihbp1⁻/⁻ mice did not restore defective TRL margination, implying that the binding of LPL to HSPGs is ineffective in promoting TRL margination. Our studies show that GPIHBP1-bound LPL is the main determinant of TRL margination.
authors.affiliation: Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Chris N
authors.initials: CN
authors.lastname: Goulbourne
authors.affiliation: Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Gin
authors.affiliation: Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Angelica
authors.initials: A
authors.lastname: Tatar
authors.affiliation: Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Chika
authors.initials: C
authors.lastname: Nobumori
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hoenger
authors.affiliation: Department of Materials, University of Oxford, Oxford OX13PH, UK.
authors.forename: Haibo
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Materials, University of Oxford, Oxford OX13PH, UK.
authors.forename: Chris R M
authors.initials: CR
authors.lastname: Grovenor
authors.affiliation: Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Oludotun
authors.initials: O
authors.lastname: Adeyo
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Esko
authors.affiliation: Department of Medicine, Columbia University, New York, NY 10032, USA.
authors.forename: Ira J
authors.initials: IJ
authors.lastname: Goldberg
authors.affiliation: Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Reue
authors.affiliation: Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Tontonoz
authors.affiliation: Division of Nutritional Science, Cornell University, Ithaca, NY 14853, USA.
authors.forename: André
authors.initials: A
authors.lastname: Bensadoun
authors.affiliation: Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Anne P
authors.initials: AP
authors.lastname: Beigneux
authors.affiliation: Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: sgyoung@mednet.ucla.edu.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Young
authors.affiliation: Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: lfong@mednet.ucla.edu.
authors.forename: Loren G
authors.initials: LG
authors.lastname: Fong
mesh_terms: D000818:Animals; D002196:Capillaries / Q000378:metabolism*; D002460:Cell Line; D042783:Endothelial Cells / Q000378:metabolism; D006321:Heart / Q000502:physiology; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008074:Lipoproteins / Q000378:metabolism*; D051379:Mice; D018110:Receptors, Lipoprotein / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism*
chemical_list: C472779:GPI-HBP1 protein, mouse; D008074:Lipoproteins; D018110:Receptors, Lipoprotein; D014280:Triglycerides; C030087:lipoprotein triglyceride; D008071:Lipoprotein Lipase
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