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Genetic analysis of molecular mechanisms of foam cell formation in atherosclerosis

Research Project

Project/Area Number 23591339
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Metabolomics
Research InstitutionJichi Medical University

Principal Investigator

OSUGA JUN-ICHI  自治医科大学, 医学部, 准教授 (10334400)

Co-Investigator(Kenkyū-buntansha) ISHIBASHI Shun  自治医科大学, 医学部, 教授 (90212919)
YAGYU Hiroaki  自治医科大学, 医学部, 非常勤講師 (60348018)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywordsマクロファージ / コレステロールエステル / 泡沫化 / 粥状動脈硬化症
Research Abstract

NCEH1 plays a principal role for cholesteryl ester hydrolase at optimal neutral pH in macrophages. Gene-knockout studies revealed that NCEH1 would have a deep relationship with foam cell formation and atherosclerotic development. In addition, it is suggested by experiments using the enzymatic inhibitor that NCEH1 might be a main enzyme in human macrophages and immunohistochemical analyses demonstrate that NCEH1 exists in the aortic area stained by anti-CD68 antibody. Furthermore oxysterols could augment the induction of apoptosis in foam cells lacking NCEH1 and advance the severity of atherosclerotic lesions. NCEH1 is a key molecule to understand the pathogenesis of atherosclerosis and lead to clinical applications including its diagnosis and treatment.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (15 results)

All 2013 2012 2011 2010 Other

All Journal Article (13 results) (of which Peer Reviewed: 13 results) Remarks (2 results)

  • [Journal Article] Macrophage lipoprotein lipase modulates the development of atherosclerosis but not adiposity2013

    • Author(s)
      Takahashi M, Yagyu H, Tazoe F, Nagashima S, Ohshiro T, Okada K, Osuga J, Goldberg IJ, Ishibashi S.
    • Journal Title

      J Lipid Res

      Volume: 54(4) Issue: 4 Pages: 1124-34

    • DOI

      10.1194/jlr.m035568

    • Related Report
      2013 Annual Research Report 2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Apolipoprotein C-II deficiency with no rare variant in the APOC2 gene2013

    • Author(s)
      Takase S, Osuga J, Fujita H, Hara K, Sekiya M, Igarashi M, Takanashi M, Takeuchi Y, Izumida Y, Ohta K, Kumagai M, Nishi M, Kubota M, Masuda Y, Taira Y, Okazaki S, Iizuka Y, Yahagi N, Ohashi K, Yoshida H, Yanai H, Tada N, Gotoda T, Ishibashi S, Kadowaki T, Okazaki H
    • Journal Title

      J Atheroscler Thromb

      Volume: 20(5)(Epub 2013 Mar 7) Pages: 481-93

    • NAID

      130004444688

    • URL

      https://www.jstage.jst.go.jp/article/jat/20/5/20_16592/_article

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Apolipoprotein C-II deficiency with no rare2013

    • Author(s)
      Takase S, Osuga J, Fujita H, Hara K, Sekiya M, Igarashi M, Takanashi M,
    • Journal Title

      J Atheroscler Thromb.

      Volume: 20 Pages: 481-93

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Liver-specific deletion of 3-hydroxy-3-methylglutaryl coenzyme A reductase causes hepatic steatosis and death.2012

    • Author(s)
      Nagashima S, Yagyu H, Ohashi K, Tazoe F, Takahashi M, Ohshiro T, Bayasgalan T, Okada K, Sekiya M, Osuga J, Ishibashi S.
    • Journal Title

      Arterioscler Thromb Vasc Biol.

      Volume: 32(8) Issue: 8 Pages: 1824-31

    • DOI

      10.1161/atvbaha.111.240754

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Current smoking status may be associated with overt albuminuria in female patients with type 1 diabetes mellitus: a cross-sectional study.2012

    • Author(s)
      Okada K, Osuga J, Kotani K, Yagyu H, Miyamoto M, Nagasaka S, Ishibashi S.
    • Journal Title

      Tob Induc Dis.

      Volume: 10 Issue: 1 Pages: 12-12

    • DOI

      10.1186/1617-9625-10-12

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ezetimibe, an inhibitor of Niemann-Pick C1-like 1 protein, decreases cholesteryl ester transfer protein in type 2 diabetes mellitus.2012

    • Author(s)
      Yagyu H, Nagashima S, Takahashi M, Miyamoto M, Okada K, Osuga J, Ishibashi S.
    • Journal Title

      Endocr J.

      Volume: 59 Pages: 1077-1084

    • NAID

      10031146718

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Molecular analysis of a novel LCAT mutation (Gly179→Arg) found in a patient with complete LCAT deficiency2011

    • Author(s)
      Wang XL, Osuga J, Tazoe F, Okada K, Nagashima S, Takahashi M, Ohshiro T, Bayasgalan T, Yagyu H, Okada K, Ishibashi S
    • Journal Title

      J Atheroscler Thromb

      Volume: 18(8)(Epub 2011 May 20) Pages: 713-9

    • NAID

      130004444539

    • URL

      https://www.jstage.jst.go.jp/article/jat/18/8/18_8003/_article

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The role of neutral cholesterol ester hydrolysis in macrophage foam cells2011

    • Author(s)
      Sekiya M, Osuga J, Igarashi M, Okazaki H, Ishibashi S
    • Journal Title

      J Atheroscler Thromb

      Volume: 18(5)(Epub 2011 Apr 6) Pages: 359-64

    • NAID

      130004845376

    • URL

      https://www.jstage.jst.go.jp/article/jat/18/5/18_7013/_article

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Urinary protein as a marker for systolic blood pressure reduction in patients with type 2 diabetes mellitus participating in an in-hospital diabetes education program.2011

    • Author(s)
      Okada K
    • Journal Title

      Hosp Pract (Minneap).

      Volume: 39 Issue: 4 Pages: 70-75

    • DOI

      10.3810/hp.2011.10.924

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Suppression of the pancreatic duodenal homeodomain transcription factor-1 (Pdx-1) promoter by sterol regulatory element-binding protein-1c (SREBP-1c)2011

    • Author(s)
      Amemiya-Kudo M, Oka J, Takeuchi Y, Okazaki H, Yamamoto T, Yahagi N, Matsuzaka K, Okazaki S, Osuga J, Yamada N, Murase T, Shimano H
    • Journal Title

      JBiol Chem

      Volume: 286 Issue: 32 Pages: 27902-14

    • DOI

      10.1074/jbc.m110.186221

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Molecular analysis of a novel LCAT mutation (Gly179 → Arg) found in a patient with complete LCAT deficiency.2011

    • Author(s)
      Wang XL
    • Journal Title

      J Atheroscler Thromb.

      Volume: 18 Pages: 713-719

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] The role of neutral cholesterol ester hydrolysis in macrophage foam cells.2011

    • Author(s)
      Sekiya M
    • Journal Title

      J Atheroscler Thromb.

      Volume: 18 Pages: 359-364

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Abrogation of neutral cholesterol ester hydrolytic activity causes adrenal enlargement2010

    • Author(s)
      Ohta K, Sekiya M, Uozaki H, Igarashi M, Takase S, Kumagai M, Takanashi M, Takeuchi Y, Izumida Y, Kubota M, Nishi M, Okazaki H, Iizuka Y, Yahagi N, Yagyu H, Fukayama M, Kadowaki T, Ohashi K, Ishibashi S, Osuga JI
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 404 Issue: 1 Pages: 254

    • DOI

      10.1016/j.bbrc.2010.11.103

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Remarks]

    • URL

      http://www.jichi.ac.jp/naika/

    • Related Report
      2013 Final Research Report
  • [Remarks]

    • URL

      http://www.jichi.ac.jp/naika/

    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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