11: THE ADENOSINE A2A RECEPTOR AGONIST UK-432,097 STIMULATES ANTI-ATHEROGENIC REVERSE CHOLESTEROL TRANSPORT PROTEINS IN THP-1 HUMAN MACROPHAGES

• Published in: Journal of investigative medicine 2016-03, Vol.64 (3), p.803
• Main Authors: Moosa, S, Voloshyna, I, Siegart, NM, De Leon, J, Carsons, SE, Kasselman, LJ, Littlefield, MJ, Reiss, AB
• Format: Article
• Language: English
• ISSN: 1081-5589; 1708-8267
• DOI: 10.1136/jim-2016-000080.11

Purpose of StudyMethotrexate (MTX) is an anti-rheumatic drug with atheroprotective properties mediated through adenosine release and activation of the adenosine A2A receptor (A2AR). A2AR ligation increases reverse cholesterol transport via upregulation of cholesterol efflux proteins ATP-binding cassette transporter (ABC)A1 and ABCG1, liver X receptor (LXR) and cholesterol 27-hydroxylase. MTX is non-specific and associated with adverse effects on liver and kidney. Therefore, this study examines the anti-atherogenic efficacy of a specific A2AR agonist, UK-432,097, a drug with an established safety profile in humans.Methods UsedTHP-1 human macrophages were incubated in the following conditions: (1) RPMI media (untreated control); (2) dimethyl sulfoxide vehicle control; (3) UK-432,097 (100 nM); (4) ZM-241385 (1 µM) (A2AR antagonist)+UK-432,097 (100 nM). Gene expression analysis was performed using QRT-PCR for cholesterol efflux genes, normalized to the housekeeping gene GAPDH. Western blotting was performed using specific antibodies. All data were analyzed by one-way ANOVA with P values