title: The Impact of Lipoprotein-Associated Oxidative Stress on Cell-Specific Microvesicle Release in Patients with Familial Hypercholesterolemia.
abstract: Objective. Microvesicles (MVs) are small cell-derived particles shed upon activation. Familial hypercholesterolemia (FH) particularly when associated with Achilles tendon xanthomas (ATX) predisposes to atherosclerosis, possibly through oxLDL-C interaction with the CD36 receptor. To investigate the hypothesis that MVs derived from cells involved in atherosclerosis are increased in FH and that CD36 expressing MVs (CD36+ MVs) may be markers of oxLDL-C-induced cell activation, cell-specific MVs were measured in FH patients with and without ATX and their association with atherogenic lipid profile was studied. Approach and Results. Thirty FH patients with and without ATX and twenty-three controls were included. Plasma concentrations of MVs and CD36+ MVs derived from platelets (PMVs), erythrocytes (ErytMVs), monocytes (MMVs), and endothelial cells (EMVs), as well as tissue factor-positive cells (TF+ MVs), were measured by flow cytometry. Total MVs, MMVs, EMVs, ErytMVs, and TF+ MVs were significantly increased in FH patients, compared to controls. CD36+ MVs derived from endothelial cells and monocytes were significantly higher in FH patients and oxLDL-C predicted all the investigated cell-specific CD36+ MVs in FH patients with ATX. Conclusions. MVs derived from cells involved in atherosclerosis were increased in FH and may contribute to elevated atherothrombosis risk. The increased cell-specific CD36+ MVs observed in FH may represent markers of oxLDL-C-induced cell activation.
authors.affiliation: Danish PhD School of Molecular Metabolism, University of Southern Denmark, 5000 Odense, Denmark; Department of Clinical Biochemistry, Aalborg University Hospital, 9000 Aalborg, Denmark.
authors.forename: M H
authors.initials: MH
authors.lastname: Nielsen
authors.affiliation: Department of Medicine and Cardiology A, Aarhus University Hospital, 8000 Aarhus, Denmark.
authors.forename: H
authors.initials: H
authors.lastname: Irvine
authors.affiliation: Department of Radiology, Aarhus University Hospital, 8000 Aarhus, Denmark.
authors.forename: S
authors.initials: S
authors.lastname: Vedel
authors.affiliation: Department of Cardiology, Aalborg University Hospital, 9000 Aalborg, Denmark.
authors.forename: B
authors.initials: B
authors.lastname: Raungaard
authors.affiliation: Department of Endocrinology M, University of Southern Denmark, 5000 Odense, Denmark.
authors.forename: H
authors.initials: H
authors.lastname: Beck-Nielsen
authors.affiliation: Department of Clinical Biochemistry, Aalborg University Hospital, 9000 Aalborg, Denmark; Department of Clinical Medicine, Faculty of Medicine, Aalborg University, 9000 Aalborg, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Handberg
mesh_terms: D000125:Achilles Tendon / Q000473:pathology; D018955:CD36 Antigens / Q000378:metabolism; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D008074:Lipoproteins / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D012044:Regression Analysis; D014973:Xanthomatosis / Q000150:complications / Q000473:pathology
chemical_list: D018955:CD36 Antigens; D008074:Lipoproteins; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein