LJ-1888, a selective antagonist for the A3 adenosine receptor, ameliorates the development of atherosclerosis and hypercholesterolemia in apolipoprotein E knock-out mice

Jong-Gil Park, Se-Jin Jeong, Jinha Yu, Gyudong Kim, Lak Shin Jeong, Goo Taeg Oh
2018 BMB Reports  
Cardiovascular diseases arising from atherosclerosis are the leading causes of mortality and morbidity worldwide. Lipid-lowering agents have been developed in order to treat hypercholesterolemia, a major risk factor for atherosclerosis. However, the prevalence of cardiovascular diseases is increasing, indicating a need to identify novel therapeutic targets and develop new treatment agents. Adenosine receptors (ARs) are emerging as therapeutic targets in asthma, rheumatoid arthritis, cancer,
more » ... hritis, cancer, ischemia, and inflammatory diseases. This study assessed whether LJ-1888, a selective antagonist for A3 AR, can inhibit the development of atherosclerosis in apolipoprotein E knock-out (ApoE −/− ) mice who are fed a western diet. Plaque formation was significantly lower in ApoE −/− mice administered LJ-1888 than in mice not administered LJ-1888, without any associated liver damage. LJ-1888 treatment of ApoE −/− mice prevented western diet-induced hypercholesterolemia by markedly reducing low-density lipoprotein cholesterol levels and significantly increasing high-density lipoprotein cholesterol concentrations. Reduced hypercholesterolemia in ApoE −/− mice administered LJ-1888 was associated with the enhanced expression of genes involved in bile acid biosynthesis. These findings indicate that LJ-1888, a selective antagonist for A3 AR, may be a novel candidate for the treatment of atherosclerosis and hypercholesterolemia. [BMB Reports 2018; 51(10): 520-525] BMB Rep. 2018; 51(10): 520-525 www.bmbreports.org
doi:10.5483/bmbrep.2018.51.10.098 fatcat:5zbfql7wbfhifgrkjwcebqv4da