Deletion of Angiotensin II Type 2 Receptor Exaggerated Atherosclerosis in Apolipoprotein E–Null Mice

DOI Web Site PubMed 被引用文献13件 オープンアクセス
  • Masaru Iwai
    From the Department of Molecular and Cellular Biology, Division of Medical Biochemistry and Cardiovascular Biology, Ehime University School of Medicine, Shitsukawa, Tohon, Ehime, Japan.
  • Rui Chen
    From the Department of Molecular and Cellular Biology, Division of Medical Biochemistry and Cardiovascular Biology, Ehime University School of Medicine, Shitsukawa, Tohon, Ehime, Japan.
  • Zhen Li
    From the Department of Molecular and Cellular Biology, Division of Medical Biochemistry and Cardiovascular Biology, Ehime University School of Medicine, Shitsukawa, Tohon, Ehime, Japan.
  • Tetsuya Shiuchi
    From the Department of Molecular and Cellular Biology, Division of Medical Biochemistry and Cardiovascular Biology, Ehime University School of Medicine, Shitsukawa, Tohon, Ehime, Japan.
  • Jun Suzuki
    From the Department of Molecular and Cellular Biology, Division of Medical Biochemistry and Cardiovascular Biology, Ehime University School of Medicine, Shitsukawa, Tohon, Ehime, Japan.
  • Ayumi Ide
    From the Department of Molecular and Cellular Biology, Division of Medical Biochemistry and Cardiovascular Biology, Ehime University School of Medicine, Shitsukawa, Tohon, Ehime, Japan.
  • Masahiro Tsuda
    From the Department of Molecular and Cellular Biology, Division of Medical Biochemistry and Cardiovascular Biology, Ehime University School of Medicine, Shitsukawa, Tohon, Ehime, Japan.
  • Midori Okumura
    From the Department of Molecular and Cellular Biology, Division of Medical Biochemistry and Cardiovascular Biology, Ehime University School of Medicine, Shitsukawa, Tohon, Ehime, Japan.
  • Li-Juan Min
    From the Department of Molecular and Cellular Biology, Division of Medical Biochemistry and Cardiovascular Biology, Ehime University School of Medicine, Shitsukawa, Tohon, Ehime, Japan.
  • Masaki Mogi
    From the Department of Molecular and Cellular Biology, Division of Medical Biochemistry and Cardiovascular Biology, Ehime University School of Medicine, Shitsukawa, Tohon, Ehime, Japan.
  • Masatsugu Horiuchi
    From the Department of Molecular and Cellular Biology, Division of Medical Biochemistry and Cardiovascular Biology, Ehime University School of Medicine, Shitsukawa, Tohon, Ehime, Japan.

書誌事項

公開日
2005-09-13
DOI
  • 10.1161/circulationaha.104.525550
公開者
Ovid Technologies (Wolters Kluwer Health)

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説明

<jats:p> <jats:bold> <jats:italic>Background—</jats:italic> </jats:bold> The role of angiotensin II (Ang II) type 2 (AT <jats:sub>2</jats:sub> ) receptor in atherosclerosis was explored with the use of AT <jats:sub>2</jats:sub> receptor/apolipoprotein E (ApoE)–double-knockout (AT <jats:sub>2</jats:sub> /ApoE-DKO) mice, with a focus on oxidative stress. </jats:p> <jats:p> <jats:bold> <jats:italic>Methods and Results—</jats:italic> </jats:bold> After treatment with a high-cholesterol diet (1.25% cholesterol) for 10 weeks, ApoE-knockout (KO) mice developed atherosclerotic lesions in the aorta. In AT <jats:sub>2</jats:sub> /ApoE-DKO mice receiving a high-cholesterol diet, the atherosclerotic changes were further exaggerated, without significant changes in plasma cholesterol level and blood pressure. In the atherosclerotic lesion, an increase in superoxide production, NADPH oxidase activity, and expression of p47 <jats:sup>phox</jats:sup> was observed. These changes were also greater in AT <jats:sub>2</jats:sub> /ApoE-DKO mice. An Ang II type 1 (AT <jats:sub>1</jats:sub> ) receptor blocker, valsartan, inhibited atherosclerotic lesion formation, superoxide production, NADPH oxidase activity, and p47 <jats:sup>phox</jats:sup> expression; these inhibitory effects were significantly weaker in AT <jats:sub>2</jats:sub> /ApoE-KO mice. We further examined the signaling mechanism of the AT <jats:sub>2</jats:sub> receptor–mediated antioxidative effect in cultured fetal vascular smooth muscle cells. NADPH oxidase activity and phosphorylation and translocation of p47 <jats:sup>phox</jats:sup> induced by Ang II were inhibited by valsartan but enhanced by an AT <jats:sub>2</jats:sub> receptor blocker, PD123319. </jats:p> <jats:p> <jats:bold> <jats:italic>Conclusions—</jats:italic> </jats:bold> These results suggest that AT <jats:sub>2</jats:sub> receptor stimulation attenuates atherosclerosis through inhibition of oxidative stress and that the antiatherosclerotic effect of valsartan could be at least partly due to AT <jats:sub>2</jats:sub> receptor stimulation by unbound Ang II. </jats:p>

収録刊行物

  • Circulation

    Circulation 112 (11), 1636-1643, 2005-09-13

    Ovid Technologies (Wolters Kluwer Health)

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