Cholesterol 27-Hydroxylase but Not Apolipoprotein apoE Contributes to A2A Adenosine Receptor Stimulated Reverse Cholesterol Transport
- 22 January 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in Inflammation
- Vol. 35 (1), 49-57
- https://doi.org/10.1007/s10753-010-9288-y
Abstract
Movement of free cholesterol between the cellular compartment and acceptor is governed by cholesterol gradients that are determined by several enzymes and reverse cholesterol transport proteins. We have previously demonstrated that adenosine A2A receptors inhibit foam cell formation and stimulate production of cholesterol 27-hydroxylase (CYP27A1), an enzyme involved in the conversion of cholesterol to oxysterols. We therefore asked whether the effect of adenosine A2A receptors on foam cell formation in vitro is mediated by CYP27A1 or apoE, a carrier for cholesterol in the serum. We found that specific lentiviral siRNA infection markedly reduced apoE or 27-hydroxylase mRNA in THP-1 cells. Despite diminished apoE expression (p < 0.0002, interferon-gamma (IFNγ) CGS vs. IFNγ alone, n = 4), CGS-21680, an adenosine A2A receptor agonist, inhibits foam cell formation. In contrast, CGS-21680 had no effect on reducing foam cell formation in CYP27A1 KD cells (4 ± 2%; p < 0.5113, inhibition vs. IFNγ alone, n = 4). Previously, we reported the A2A agonist CGS-21680 increases apoAI-mediated cholesterol efflux nearly twofold in wild-type macrophages. Adenosine receptor activation had no effect on cholesterol efflux in CYP27A1 KD cells but reduced efflux in apoE KD cells. These results demonstrate that adenosine A2A receptor occupancy diminishes foam cell formation by increasing expression and function of CYP27A1.Keywords
This publication has 18 references indexed in Scilit:
- A2A adenosine receptor stimulation decreases foam cell formation by enhancing ABCA1-dependent cholesterol effluxJournal of Leukocyte Biology, 2010
- A BRIEF COMMUNICATIONExperimental Biology and Medicine, 2009
- Atheroprotective effects of methotrexate on reverse cholesterol transport proteins and foam cell transformation in human THP‐1 monocyte/macrophagesArthritis & Rheumatism, 2008
- The many intersecting pathways underlying apolipoprotein B secretion and degradationTrends in Endocrinology & Metabolism, 2008
- Cholesterol efflux pathways and other potential mechanisms involved in the athero‐protective effect of high density lipoproteinsJournal of Internal Medicine, 2008
- Apolipoprotein E RecyclingArteriosclerosis, Thrombosis, and Vascular Biology, 2006
- Cellular localization and interaction of ABCA1 and caveolin-1 in aortic endothelial cells after HDL incubationBiochemical and Biophysical Research Communications, 2005
- Adenosine A2A receptor occupancy stimulates expression of proteins involved in reverse cholesterol transport and inhibits foam cell formation in macrophagesJournal of Leukocyte Biology, 2004
- 27-Hydroxycholesterol Is an Endogenous Ligand for Liver X Receptor in Cholesterol-loaded CellsJournal of Biological Chemistry, 2001
- Sterol 27-Hydroxylase– and ApoAI/Phospholipid–Mediated Efflux of Cholesterol From Cholesterol-Laden MacrophagesArteriosclerosis, Thrombosis, and Vascular Biology, 1998