Abstract P265: Adenosine 2A Receptor Activation Regulates Expression of Scavenger Receptors CD36 and LOX-1 in Human Macrophages and Aortic Endothelial Cells
Objectives of the study. A variety of scavenger receptors (SR) have been linked to lipid accumulation in the vasculature. Among these, CD36 and LOX-1 are proposed to play a prominent role in atherosclerosis. Adenosine is a potent cellular signaling molecule with anti-atherogenic properties. Our previous work has shown that agonists specific for the adenosine A2A receptor (A2AR) enhance cholesterol efflux, preventing macrophage foam cell transformation. Here we report additional atheroprotective effects of A2AR activation through changes in SR expression.
Methods. Primary human aortic endothelial cells (HAECs) and THP-1 human macrophages were incubated in the presence of oxLDL (20 μg/ml) and: a) growth media b) DMSO vehicle c) the A2AR agonist CGS-21680 (1 μM) d) the A2AR antagonist ZM-241385 (10 μM, 1h) + CGS-21680 (1 μM) (n=5). SR expression was evaluated by real-time PCR. PCR results were confirmed by immunofluorescence analysis with CD36 and LOX-1-specific primary antibodies, followed by incubation with FITC conjugated secondary antibodies.
Results. CGS-21680 downregulated CD36 and LOX-1 expression vs. untreated HAEC (67.89±9.55% and 49.00±2.55%, respectively, n=6, P<0.01). This effect was abrogated by ZM-241385, resulting in upregulation of these SR to 175.9±22.67% and 172.10±39.6%, respectively, vs. control (n=6, P<0.001). The pattern of SR expression changes in THP-1 macrophages upon exposure to CGS-21680 and ZM-241385 was the same as in HAEC. PCR results were confirmed by quantization of fluorescence intensity with immunofluorescence confocal microscopy.
Summary. A2AR activation is a promising therapeutic approach to prevent lipid overload in arterial vasculature. Our data support an anti-atherogenic role for the A2AR in both cholesterol influx and efflux pathways. Several new agents that target the A2AR are in development and they may hold promise as treatment for atherosclerotic cardiovascular disease.
- © 2011 by American Heart Association, Inc.