title: Overexpression of apolipoprotein O does not impact on plasma HDL levels or functionality in human apolipoprotein A-I transgenic mice.
abstract: Apolipoprotein (apo) O is a newly discovered apolipoprotein preferentially contained within HDL; however, currently, no data are available on the (patho)physiological effects of apoO. Therefore, the present study assessed the impact of apoO overexpression on (i) plasma lipids and lipoproteins as well as on (ii) HDL functionality. Human apoO was overexpressed by means of recombinant adenovirus (AdhapoO) in human apoA-I transgenic mice, a humanized mouse model of HDL metabolism. AdhapoO substantially increased apoO in plasma and within HDL. However, plasma triglycerides, phospholipids, total cholesterol and HDL cholesterol did not change. HDL size distribution, lipid composition and the apoA-I and the apoO distribution over the different HDL fractions separated by FPLC remained unaltered. Furthermore, enrichment of HDL with apoO did not impact on HDL functionality assessed in four independent ways, namely (i) stimulation of cholesterol efflux from macrophage foam cells, (ii) protection against LDL oxidation, (iii) anti-inflammatory activity on endothelial cells, and (iv) induction of vasodilation in isolated aortic rings ex vivo as a measure of stimulating vascular NO production. These results demonstrate that although overexpression of apoO results in a substantial enrichment of HDL particles with this novel apolipoprotein, apoO does not impact the plasma lipoprotein profile or HDL functionality.
authors.affiliation: Department of Pediatrics, Center for Liver, Digestive and Metabolic Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Niels
authors.initials: N
authors.lastname: Nijstad
authors.forename: Jan Freark
authors.initials: JF
authors.lastname: de Boer
authors.forename: William R
authors.initials: WR
authors.lastname: Lagor
authors.forename: Markus
authors.initials: M
authors.lastname: Toelle
authors.forename: David
authors.initials: D
authors.lastname: Usher
authors.forename: Wijtske
authors.initials: W
authors.lastname: Annema
authors.forename: Markus van
authors.initials: Mv
authors.lastname: der Giet
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Rader
authors.forename: Uwe J F
authors.initials: UJ
authors.lastname: Tietge
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D016632:Apolipoprotein A-I / Q000502:physiology*; D001053:Apolipoproteins / Q000378:metabolism*; D002478:Cells, Cultured; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000737:chemistry*; D000229:Dependovirus / Q000235:genetics; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008055:Lipids / Q000097:blood*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010084:Oxidation-Reduction; D014471:Umbilical Veins / Q000166:cytology / Q000378:metabolism; D014664:Vasodilation
chemical_list: D016632:Apolipoprotein A-I; D001053:Apolipoproteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008055:Lipids