Genetic analysis of molecular mechanisms of foam cell formation in atherosclerosis

• Project/Area Number: 23591339
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Jichi 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: ¥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.

Research Products

• [Journal Article] Macrophage lipoprotein lipase modulates the development of atherosclerosis but not adiposity (2013)
  • 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
  • Peer Reviewed
• [Journal Article] Apolipoprotein C-II deficiency with no rare variant in the APOC2 gene (2013)
  • 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
  • Peer Reviewed
• [Journal Article] Apolipoprotein C-II deficiency with no rare (2013)
  • 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
  • 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
  • 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
  • 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
  • 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, 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
  • Peer Reviewed
• [Journal Article] The role of neutral cholesterol ester hydrolysis in macrophage foam cells (2011)
  • 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
  • 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
  • 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
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] Abrogation of neutral cholesterol ester hydrolytic activity causes adrenal enlargement (2010)
  • 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
  • Peer Reviewed
• [Remarks]
  • URL: http://www.jichi.ac.jp/naika/
• [Remarks]
  • URL: http://www.jichi.ac.jp/naika/