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Regulation of macrophage foam cell formation and atherosclerosis by novel regulatory peptides for cardiovascular system

Research Project

Project/Area Number 20591084
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionShowa University

Principal Investigator

MIYAZAKI Akira  Showa University, 医学部, 教授 (70253721)

Co-Investigator(Kenkyū-buntansha) WATANABE Takuya  東京薬科大学, 生命科学部, 教授 (30297014)
HIRANO Tsutomu  昭和大学, 医学部, 教授 (00167610)
Co-Investigator(Renkei-kenkyūsha) SHICHIRI Masayoshi  北里大学, 医学部, 教授 (10206097)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords動脈硬化 / 血管作動性物質 / マクロファージ / 高血圧 / 単球 / 内皮細胞 / サリューシン / 接着分子 / 蛋白質 / コレステロール / 酵素
Research Abstract

Continuous subcutaneous infusion of urotensin II, a strong vasoconstrictor peptide, enhanced atherosclerotic lesions by 8-fold in fat-fed apoE-knockout mice. Analyses of peritoneal macrophages from urotensin II-treated mice revealed 7-fold increase in foam cell formation induced by oxidized LDL. Salusins are novel vasoregulatory peptides that derive from the same precursor. Development of atherosclerosis in apoE-KO mice was suppressed by 68% by continuous subcutaneous infusion of salusin-α but was 2.6-fold enhanced by salusin-β. Peritoneal macrophages from salusin?α-treated mice revealed 68% reduction in foam cell formation induced by oxidized LDL whereas macrophages from salusin-β-treated mice showed 2.6-fold increase in foam cell formation. Thus, urotensin II and salusins can be regarded as novel therapeutic targets for atherosclerosis.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (32 results)

All 2011 2010 2009 2008 2005

All Journal Article (18 results) (of which Peer Reviewed: 18 results) Presentation (14 results)

  • [Journal Article] Hic-5 deficiency enhances mechanosensitive apoptosis and modulates vascular remodeling2011

    • Author(s)
      Kim-Kaneyama JR, et al.
    • Journal Title

      Journal of Molecular and Cellular Cardiology

      Volume: 50 Pages: 77-86

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chronic infusin of salusin-α and salusin-β exerts opposite effects on atherosclerostic lesion development in apolipoprotein E-deficient mice.2010

    • Author(s)
      Nagashima M, Watanabe T, Shiraishi Y, Morita R, Terasaki M, Arita S, Hongo S, Sato K, Shichiri M, Miyazaki A, Hirano T
    • Journal Title

      Atherosclerosis 212(1)

      Pages: 70-77

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] A selective ACAT-1 inhibitor, K-604, stimulates collagen production in cultured smooth muscle cells and alters plaque phenotype in apolipoprotein E-knockout mice.2010

    • Author(s)
      Yoshinaka Y, Shibata H, Kobayashi H, Kuriyama H, Shibuya K, Tanabe S, Watanabe T, Miyazaki A
    • Journal Title

      Atherosclerosis 213(1)

      Pages: 85-91

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chronic infusin of salusin-α and salusin-β exerts opposite effects on atherosclerostic lesion development in apolipoprotein E-deficient mice2010

    • Author(s)
      Nagashima M, et al.
    • Journal Title

      Atherosclerosis

      Volume: 212 Pages: 70-77

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A selective ACAT-1 inhibitor, K-604, stimulates collagen production in cultured smooth muscle cells and alters plaque phenotype in apolipoprotein E-knockout mice2010

    • Author(s)
      Yoshinaka Y, et al.
    • Journal Title

      Atherosclerosis

      Volume: 213 Pages: 85-91

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increased plasma urotensin-II and carotid atherosclerosis are associated with vascular dementia.2009

    • Author(s)
      Ban Y, Watanabe T, Suguro T, Matsuyama T, Iso Y, Sakai T, Sato R, Idei T, Nakano Y, Ota H, Miyazaki A, Kato N, Hirano T, Ban Y, Kobayashi Y
    • Journal Title

      Journal of Atherosclerosis and Thrombosis 16(3)

      Pages: 179-187

    • NAID

      10025765398

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Leptin modulates ACAT-1 expression and cholesterol efflux from human macrophages.2009

    • Author(s)
      Hongo S, Watanabe T, Arita S, Kanome T, Kageyama H, Shioda S, Miyazaki A
    • Journal Title

      American Journal of Physiology, Endocrinology and Metabolism 297(2)

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Preventive effects of heregulin-β1 on macrophage foam cell formation and atherosclerosis.2009

    • Author(s)
      Xu G, Watanabe T, Iso Y, Koba S, Sakai T, Nagashima M, Arita S, Hongo S, Ota H, Kobayashi Y, Miyazaki A, Hirano T
    • Journal Title

      Circulation Research 105(5)

      Pages: 500-510

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Human Urotensin II promotes hypertension and atherosclerotic cardiovascular diseases (review).2009

    • Author(s)
      Watanabe T, Arita S, Shiraishi Y, Suguro T, Sakai T, Hongo S, Miyazaki A
    • Journal Title

      Current Medicinal Chemistry 16(5)

      Pages: 550-563

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Increased urotensin-II and carotid atherosclerosis are asociated with vascular dementia2009

    • Author(s)
      Ban Y, et al.
    • Journal Title

      Journal of Atherosclerosis and Thrombosis 16

      Pages: 179-187

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Leptin modulates ACAT-1 expression and cholesterol efflux from human macrophages2009

    • Author(s)
      Hongo S, et al.
    • Journal Title

      American Journal of Physiology 297

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Angiotensin II upregulates acyl-CoA : cholesterol acyltransferase-1 via AT1 receptor in human monocyte-macrophages.2008

    • Author(s)
      Kanome T, Watanabe T, Nishio K, Takahashi K, Hongo S, Miyazaki A
    • Journal Title

      Hypertension Research 31(9)

      Pages: 1801-1810

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chronic urotensin II infusion enhances macrophage foam cell formation and atherosclerosis in apolipoprotein E-knockout mice.2008

    • Author(s)
      Shiraishi Y, Watanabe T, Suguro T, Kato R, Hongo S, Itabe H, Miyazaki A, Hirano T, Adachi M
    • Journal Title

      Journal of Hypertension 26(10)

      Pages: 1955-1965

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Increased plasma urotensin-II levels are associated with diabetic retinopathy and carotid atherosclerosis in type 2 diabetes mellitus.2008

    • Author(s)
      Suguro T, Watanabe T, Kodate S, Xu G, Hirano T, Adachi M, Miyazaki A
    • Journal Title

      Clinical Science 115(11)

      Pages: 327-334

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chronic urotensin II infusion enhances macrophage foam cell formation and atherosclerosis in apolipoprotein E-knockout mice.2008

    • Author(s)
      Shiraishi Y
    • Journal Title

      Jouranl of Hypertension 26

      Pages: 1955-1965

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increased plasma urotensin-II levels are associated with diabetic retinopiathy and carotid atherosclerosis in type 2 diabetes mellitus.2008

    • Author(s)
      Suguro T
    • Journal Title

      Clinical Science 115

      Pages: 327-334

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Angiotensin II upregulates acyI-Co A : cholesterol acyltransferase-1 via ATI receptor in human monocyte-macrophages.2008

    • Author(s)
      Kanome T
    • Journal Title

      Hypertension Research 31

      Pages: 1801-1810

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Preventive effects of heregulin-betal on macrophage foam cell formation and atherosclerosis2005

    • Author(s)
      Xu G, et al.
    • Journal Title

      Circulation Research 105

      Pages: 500-510

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Hic-5 deficiency enhances mechanosensitive apoptosis and modulates vascular remodeling2010

    • Author(s)
      Shuri Kaneyama, et al.
    • Organizer
      第42回日本動脈硬化学会学術集会
    • Place of Presentation
      長良川国際会議場
    • Year and Date
      2010-07-15
    • Related Report
      2010 Annual Research Report
  • [Presentation] Preventive effects of heregulin-β1 on macrophage foam cell formation and atherosclerosis.2010

    • Author(s)
      渡部琢也・有田茂子・長嶋理晴・平野勉・宮崎章・他
    • Organizer
      第42回日本動脈硬化学会学術集会
    • Place of Presentation
      岐阜
    • Related Report
      2010 Final Research Report
  • [Presentation] ヒトマクロファージからのコレステロール搬出に対するレプチンの抑制作用2009

    • Author(s)
      本郷茂樹, ほか
    • Organizer
      第51回日本脂質生化学会
    • Place of Presentation
      ウィル愛知
    • Year and Date
      2009-07-31
    • Related Report
      2009 Annual Research Report
  • [Presentation] Chronic infusion of salusin-α and -β exerts opposite effects on atherosclerotic lesion development in apolipoprotein E-knockout mice.2009

    • Author(s)
      長嶋理晴・渡部琢也・宮崎 章・平野勉
    • Organizer
      第41回日本動脈硬化学会学術集会
    • Place of Presentation
      下関
    • Related Report
      2010 Final Research Report
  • [Presentation] ヒトマクロファージからのコレステロール搬出に対するレプチンの抑制作用2009

    • Author(s)
      本郷茂樹・渡部琢也・有田茂子・金山朱里・宮崎章
    • Organizer
      第51回日本脂質生化学会
    • Place of Presentation
      名古屋
    • Related Report
      2010 Final Research Report
  • [Presentation] Opposite effects of salusins on the development of atherosclerotic plaques.2009

    • Author(s)
      Watanabe T, Nagashima M, Arita S, Hongo S, Shichiri M, Hirano T, Miyazaki A
    • Organizer
      American Heart Association Scientific Sessions 2009
    • Place of Presentation
      Orlando
    • Related Report
      2010 Final Research Report
  • [Presentation] 血漿ウロテンシンII濃度の増加と糖尿病性網膜症および頚動脈硬化との関連2008

    • Author(s)
      勝呂 俊昭
    • Organizer
      第40回日本動脈硬化学会学術集会
    • Place of Presentation
      つくば国際会議場
    • Year and Date
      2008-07-10
    • Related Report
      2008 Annual Research Report
  • [Presentation] 血漿ウロテンシンII(UII)濃度の増加と糖尿病性網膜症との関連2008

    • Author(s)
      勝呂俊昭・渡部琢也・宮崎 章・平野勉・他
    • Organizer
      第51回日本糖尿病学会年次学術集会
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report
  • [Presentation] ウロテンシンIIの血中レベルの増加は血管性認知症の危険因子である2008

    • Author(s)
      伴良行・渡部琢也・宮崎章・他
    • Organizer
      第51回日本糖尿病学会年次学術集会
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report
  • [Presentation] ヒト単球由来マクロファージの泡沫化に対するサリューシンαおよびβの相反作用2008

    • Author(s)
      宮崎章・本郷茂樹・渡部琢也
    • Organizer
      第50回日本脂質生化学会
    • Place of Presentation
      徳島
    • Related Report
      2010 Final Research Report
  • [Presentation] 血漿ウロテンシンII(UII)濃度の増加と糖尿病性網膜症および頸動脈硬化との関連2008

    • Author(s)
      勝呂俊昭・渡部琢也・宮崎章・平野勉, 他
    • Organizer
      第40回日本動脈硬化学会学術集会
    • Place of Presentation
      つくば
    • Related Report
      2010 Final Research Report
  • [Presentation] ウロテンシンIIの血中レベルの増加は血管性認知症の危険因子である2008

    • Author(s)
      伴良行・渡部琢也・宮崎章・他
    • Organizer
      第40回日本動脈硬化学会学術集会
    • Place of Presentation
      つくば
    • Related Report
      2010 Final Research Report
  • [Presentation] Preventive effects of heregulin-β1 on macrophage foam cell formation and atherosclerosis.2008

    • Author(s)
      Watanabe T, Arita S, Hongo S, Miyazaki A, 他
    • Organizer
      American Heart Association Scientific Sessions 2008
    • Place of Presentation
      New Orleans
    • Related Report
      2010 Final Research Report
  • [Presentation] 新規血管作動性物質サリューシンαおよびβのマクロファージ泡沫化および動脈硬化に対する相反作用2008

    • Author(s)
      渡部琢也・有田茂子・本郷茂樹・宮崎章
    • Organizer
      第81回日本生化学会大会、第31回日本分子生物学会年会合同大会
    • Place of Presentation
      神戸
    • Related Report
      2010 Final Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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