LJ-1888, a selective antagonist for the A(3) adenosine receptor, ameliorates the development of atherosclerosis and hypercholesterolemia in apolipoprotein E knock-out mice
- 주제(키워드) Atherosclerosis , High-density lipoprotein cholesterol (HDL-chol) , Hypercholesterolemia , Low-density lipoprotein cholesterol (LDL-chol) , LJ-1888
- 주제(기타) Biochemistry & Molecular Biology
- 설명문(일반) [Park, Jong-Gil] KRIBB, Biotherapeut Translat Res Ctr, Daejeon 34141, South Korea; [Jeong, Se-Jin] Washington Univ, Sch Med, Dept Med, Div Cardiovasc, St Louis, MO 63110 USA; [Yu, Jinha; Kim, Gyudong; Jeong, Lak Shin] Seoul Natl Univ, Coll Pharm, Seoul 08826, South Korea; [Oh, Goo Taeg] Ewha Womans Univ, Dept Life Sci, Immune & Vasc Cell Network Res Ctr, Natl Creat Initiat, Seoul 03760, South Korea
- 등재 SCIE, SCOPUS, KCI등재
- 발행기관 KOREAN SOCIETY BIOCHEMISTRY & MOLECULAR BIOLOGY
- 발행년도 2018
- URI http://www.dcollection.net/handler/ewha/000000156106
- 본문언어 영어
- Published As http://dx.doi.org/10.5483/BMBRep.2018.51.10.098
- 저작권 이화여자대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
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 II-1888, a selective antagonist for A(3) 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 II-1888 than in mice not administered II-1888, without any associated liver damage. II-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 II-1888 was associated with the enhanced expression of genes involved in bile acid biosynthesis. These findings indicate that II-1888, a selective antagonist for A(3) AR, may be a novel candidate for the treatment of atherosclerosis and hypercholesterolemia.
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