title: Severity of hyperlipidemia does not affect antiatherosclerotic effect of an angiotensin II receptor antagonist in apolipoprotein E-deficient mice.
abstract: The purpose of this study was to clarify whether severity of hyperlipidemia affects the antiatherosclerotic effect of angiotensin II receptor blockers (ARBs). The effect of olmesartan medoxomil, an ARB, on atherosclerotic lesion was examined in apolipoprotein E-deficient (ApoEKO) mice fed a normal diet (ND) or a high-fat-supplemented diet (FD) for 25 weeks. ApoEKO mice have high plasma cholesterol levels, which were further increased by feeding of an FD. Both the atherosclerotic lesion area of the aortic luminal surface and the atherosclerotic lesion thickness in the aortic valves were significantly greater in the FD mice than in the ND mice. Olmesartan medoxomil did not affect the plasma cholesterol levels in either the ND or FD ApoEKO mice; however, it reduced effectively both the atherosclerotic lesion surface area and the lesion thickness even in FD ApoEKO mice. It is concluded that the antiatherosclerotic effect of ARBs is not weakened by the high plasma cholesterol level, suggesting the usefulness of ARBs in the treatment of atherosclerosis, even in a situation in which the plasma cholesterol level is not fully controlled.
authors.affiliation: Pharmacology and Molecular Biology Research Laboratories, Sankyo Co, Ltd, Tokyo, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Kato
authors.forename: Toshio
authors.initials: T
authors.lastname: Sada
authors.forename: Hiroko
authors.initials: H
authors.lastname: Chuma
authors.forename: Makoto
authors.initials: M
authors.lastname: Mizuno
authors.forename: Hideki
authors.initials: H
authors.lastname: Terashima
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Fukushima
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Koike
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001011:Aorta / Q000473:pathology; D001021:Aortic Valve / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D001794:Blood Pressure; D002784:Cholesterol / Q000097:blood; D006339:Heart Rate; D006949:Hyperlipidemias / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000068557:Olmesartan Medoxomil; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001057:Apolipoproteins E; D007093:Imidazoles; D013777:Tetrazoles; D014280:Triglycerides; D000068557:Olmesartan Medoxomil; D002784:Cholesterol