Adenovirus-mediated gene transfer of Lp-PLA2 reduces LDL degradation and foam cell formation in vitro.

Journal of Lipid Research
Päivi TurunenSeppo Ylä-Herttuala

Abstract

Oxidation of LDL generates biologically active platelet-activating factor (PAF)-like phospholipid derivatives, which have potent proinflammatory activity. These products are inactivated by lipoprotein-associated phospholipase A2 (Lp-PLA2), an enzyme capable of hydrolyzing PAF-like phospholipids. In this study, we generated an adenovirus (Ad) encoding human Lp-PLA2 and injected 10(8), 10(9), and 10(10) plaque-forming unit doses of Adlp-PLA2 and control AdlacZ intra-arterially into rabbits to achieve overexpression of Lp-PLA2 in liver and in vivo production of Lp-PLA2-enriched LDL. As a result, LDL particles with 3-fold increased Lp-PLA2 activity were produced with the highest virus dose. Increased Lp-PLA2 activity in LDL particles decreased the degradation rate in RAW 264 macrophages after standard in vitro oxidation to 60-80% compared with LDL isolated from LacZ-transduced control rabbits. The decrease was proportional to the virus dose and Lp-PLA2 activity. Lipid accumulation and foam cell formation in RAW 264 macrophages were also decreased when incubated with oxidized LDL containing the highest Lp-PLA2 activity. Inhibition of the Lp-PLA2 activity in the LDL particles led to an increase in lipid accumulation and foam cell for...Continue Reading

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Citations

Jan 17, 2012·Journal of Clinical Immunology·Zohara SternbergFrederick E Munschauer
Mar 22, 2012·The Journal of Biological Chemistry·Calivarathan LatchoumycandaneThomas M McIntyre
Feb 18, 2005·Current Opinion in Clinical Nutrition and Metabolic Care·Ewa Ninio
Mar 25, 2010·Journal of Lipid Research·Konstantinos P MarkakisEleni E Kotsifaki
Oct 8, 2008·Journal of Lipid Research·Thomas M McIntyreDiana M Stafforini
Jun 26, 2007·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Shao-Yan ZhangToru Nabika
Dec 3, 2014·Biochimica Et Biophysica Acta·Carlos GuijasJesús Balsinde
Aug 1, 2015·International Journal of Molecular Sciences·Peiqiu CaoZhengquan Su
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Apr 23, 2008·Circulation·Anna-Liisa LevonenSeppo Ylä-Herttuala

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