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Adenosine A2A Receptor Agonists Regulate Cholesterol Homeostasis in Mouse Bone Marrow Derived Macrophages (BMDM)
Author(s) -
Voloshyna Iryna,
Littlefield Michael J,
Kaplan Laura,
Rieger Jayson M,
Figler Robert,
Reiss Allison B
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.822.1
Subject(s) - abca1 , cd36 , scavenger receptor , abcg1 , chemistry , medicine , endocrinology , cholesterol , agonist , apolipoprotein e , adenosine a2a receptor , receptor , adenosine , apolipoprotein b , pharmacology , adenosine receptor , biology , lipoprotein , biochemistry , transporter , disease , gene
Objective Adenosine A 2A receptor (A 2A R) mediate anti‐inflammatory changes in the vasculature. Here we report that A 2A R ligation via administration of the specific agonist ATL313 or the adenosine‐releasing drug methotrexate (MTX) to apolipoprotein (apo) E −/− mice enhances expression of cholesterol efflux proteins: cholesterol 27‐hydroxylase and ATP binding cassette transporter (ABC) A1 and reduces scavenger receptor expression in BMDM. Methods Male homozygous apoE −/− (C57BL/6J) mice were randomized into 3 groups (n=8) and fed from age 10–20 weeks: regular chow [control], ATL313 300 μg/kg/day [AEA] or MTX 1mg/kg/week [AEM]. Femurs were dissected and cell suspensions obtained by flushing bones with DMEM. BMDM were generated by culturing cells for 7 days with MCSF. Expression of F40/80, ABCA1 and G1, 27‐hydroxylase, CD36 and LOX1 were evaluated by QRT‐PCR. Western blot confirmed results of PCR. Results In apoE −/− mice, A 2A R activation raises 27‐hydroxylase mRNA (by 23.5±3.5% in AEA and 18.7±2.1% in AEM) and ABCA1 (by 38.9±5.4% in AEA and 45.7±8.3% in AEM). ABCG1 expression was unchanged. CD36 and LOX‐1 mRNA were downregulated in both AEA and AEM groups, compared to control. Conclusions A 2A R ligation has an anti‐atherogenic effect on cholesterol transport that prevents lipid accumulation. Novel therapeutic approaches to cardioprotection may be directed toward improved cholesterol balance through A 2A R activation.