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

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

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, 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.

Original languageEnglish
Pages (from-to)520-525
Number of pages6
JournalBMB Reports
Volume51
Issue number10
DOIs
StatePublished - 1 Oct 2018

Bibliographical note

Publisher Copyright:
© 2018 by the The Korean Society for Biochemistry and Molecular Biology.

Keywords

  • Atherosclerosis
  • High-density lipoprotein cholesterol (HDL-chol)
  • Hypercholesterolemia
  • LJ-1888
  • Low-density lipoprotein cholesterol (LDL-chol)

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