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A novel monoclonal antibody recognizing extracellular space of the atherosclerotic lesions in WHHL rabbits.

Research Project

Project/Area Number 03454495
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionTeikyo University

Principal Investigator

TAKANO Tatsuya  Teikyo Univ., Fac. of Pharm. Sci., Professor, 薬学部, 教授 (40124995)

Co-Investigator(Kenkyū-buntansha) EYA Seiji  Teikyo Univ., Fac. of Pharm. Sci., Research Associate, 薬学部, 助手 (20221814)
MORI Masahiro  Teikyo Univ., Fac. of Pharm. Sci., Research Associate, 薬学部, 助手 (00230079)
ITABE Hiroyuki  Teikyo Univ., Fac. of Pharm. Sci., Research Associate, 薬学部, 助手 (30203079)
MINEO Chieko  Teikyo Univ., Fac. of Pharm. Sci., Research Associate, 薬学部, 助手 (00190710)
IMANAKA Tsuneo  Teikyo Univ., Fac. of Pharm. Sci., Assistant Professor, 薬学部, 講師 (50119559)
柳生 靖子  帝京大学, 薬学部, 助手 (60211611)
Project Period (FY) 1991 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 1993: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1992: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1991: ¥3,000,000 (Direct Cost: ¥3,000,000)
Keywordsatherosclerosis / glycoprotein / vitronectin / extracellular matrix / cholesterol / ピトロネクチン / コレステロール・エステル / モノクロナル抗体 / シアル酸 / コレステロ-ル / cDNA
Research Abstract

In order to study the mechanisms of cholesteryl ester accumulation in the extracellular space of the atherosclerotic aorta, we prepared novel monoclonal antibodies against atherosclerotic lesions using a delipidated crude homogenate of atherosclerotic aorta from Watanabe-heritable hyperlipidemic (WHHL) rabbits as a complex mixture of immunogens. By screening the antibodies histochemically, we were able to obtain for the first time monoclonal antibodies which specifically recognized the extracellular matrix with lipid-laden deposits (EMRla/212D) in atherosclerotic lesions. The purified antigenic material is a glycoprotein with a molecular mass of 66 kDa, and the epitope of the antigenic material contains sialic acid as a major element.
We have isolated from rabbit liver cDNA library clones coding for the 66-kDa glycoprotein (GP66). The clone spans the sequence coding for the entire GP66 (456 amino acids) and 19 amino acids of a signal peptide. GP66 was deduced to be rabbit vitronectin from its nucleotide sequence, containing an Arg-Gly-Asp cell attachment sequence and showing 76% amino acid sequence homology with human vitronectin. Furthermore, EMRla/212D recognized rabbit vitronectin purified by heparin affinity chromatography. RNA blot hybridization detected one transcript of the same size in normal and WHHL rabbit liver. The levels of plasma GP66 and liver GP66 mRNA were not altered, whereas 9-fold greater accumulation of GP66 was observed in the thoracic aorta of WHHL rabbit. These results suggest that GP66 is rabbit vitronectin, which selectively accumulates in the atherosclerotic aorta with the development of atherosclerosis.

Report

(4 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • 1991 Annual Research Report
  • Research Products

    (40 results)

All Other

All Publications (40 results)

  • [Publications] K.Magari,H.Fukushima,et al.: "Platelst adhesion to a biomimetic prosthesis prepared from canine arterial wall." Artif.Argans. 15(6). 492-497 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Y.Yagyu,R.Hashida,et.al.: "Effect of PGI_2 on platelet binding to partially denuded endothelial monolayer in vitro." Thromb.Res.64. 733-744 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Y.Yagyu,C.Mineo,et al.: "Intercellular transport through a partially denuded arterial endothelial monolayer.Effects of platelets and PGI_2." Thromb.Res.66. 215-222 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] C.Mineo,T.Kanaseki,et al.: "Hydrolysis of lipid droplets in acid cholesteryl-esterase deficient fibroblasts." Cell Struct.Funct.17. 191-196 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] T.Takano: "Accumulation of cholesteryl ester in atherosclerotic lesions." Acta Pathol.Jpn.42(9). 625-631 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] T.Takano,H.Mowti,et al.: "Peroxidized lipoproteins in atherosclerotic lesions detected by a monoclonal antibody." Active Oxygens,Lipid Peroxides,and Antioxidants. 139-148 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 高野達哉: "^<nano>GIGA(マクロファージと動脈硬化)" 日本臨牀社, 6 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 高野達哉: "日本血管外科学会雑誌(動脈硬化発症における内皮機能)" 日本血管外科学会, 8 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Imanaka, T., Lazarow, P.B.and Takano, T.: "A novel 57 kDa peroxisomal membrane polypeptide detected by monclonal antibody (PXMla/207B)." Biochim. Biophys. Acta. 1062. 264-270 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Magari, K., Fukushima, H., Ishimaru, S., Furukawa, K, Yagyu, Y.and Takano, T.: "Platelet adhesion to a biomimetic prosthesis prepared from canine arterial wall." Artif. Organs. 15(6). 492-497 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yagyu, Y., Hashida, R., Iwasaki, K., Mineo, C., Imanaka, T.and Takano, T.: "Effect of PGI_2 on platelet binding to partially denuded endothelial monolayr in vitro." Thromb. Res.64. 733-744 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Imanaka, T., Lazarow, P.B.and Takano, T.: "Suramin prevents import of acyl-CoA oxidase into rat liver peroxisomes." Biochim. Biophys. Acta. 1134. 197-202 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yagyu, Y., Mineo, C., Imanaka, T., Ikegami, S.and Takano, T.: "Intercellular transport through a partially denuded arterial endothelial monolayr. Effects of platelets and PGI_2." Thromb. Res.66. 215-222 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mineo, C., Kanaseki, T., Imanaka, T.and Takano, T.: "Hydrolysis of lipid droplets in acid cholesteryl-esterase-deficient fibroblasts." Cell Struct. Funct.17. 191-196 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Simizu, S., Imanaka, T., Takano, T.and Ohkuma, S.: "Induction and characterization of two types of ATPase on rat liver peroxisomes." J.Biochem.112(3). 376-384 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Shimizu, S., Imanaka, T., Takano, T.and Ohkuma, S.: "Major ATPases on clofibrate-inducted rat liver peroxisomes are not associated with 70 kDa peroxisomal membrane protein (PMP70)." J.Biochem.112(6). 733-736 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Takano, T.: "Accumulation of cholesteryl ester in atherosclerotic lesions." Acta Pathol. Jpn.42(9). 625-631 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Imanaka, T., Shiina, Y., Moriyama, Y., Ohkuma, S.and Takano, T.: "Immunological detection of F_1-ATPase gamma-subunit in rat liver peroxisomes." Biochem. Biophys. Res. Commun.195(2). 1027-1034 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Takano, T., Mowri, H.and Itabe, H.: "Peroxidized lipoproteins in atherosclerotic lesions detected by a monoclonal antibody." Active Oxygens, Lipid Peroxides, and Antioxidants. 139-148 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] K.Magari,H.Fukushima,S.Ishimaru,et al.: "Platelet adhesion to a biomimetic prosthesis prepared from canine arterial wall." Artif.Organs. 15(6). 492-497 (1991)

    • Related Report
      1993 Annual Research Report
  • [Publications] Y.Yagyu,R.Hashida,K.Iwasaki,et al.: "Effect of PGI_2 on platelet binding to partially denuded endothelial monolayer in vitro." Thromb.Res.64. 733-744 (1991)

    • Related Report
      1993 Annual Research Report
  • [Publications] Y.Yagvu,C.Mineo,T.Imanaka,et al.: "Intercellular transport through a partially denuded arterial endothelial monolayer.Effects on platelets and PGI_2." Thromb.Res.66. 215-222 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] C.Mineo,T.Kanaseki,T.Imanaka,et al.: "Hydrolysis of lipid droplets in acid cholesteryl-esterase-deficient fibroblasts." Cell Struct.Funct.17. 191-196 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] T.Takano: "Accumilation of cholesteryl ester in atherosclerotic lesions." Acta Pathol.Jpn.42(9). 625-631 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] T.Takano,H.Mowri,&H.Itabe: "Peroxidized lipoproteins in atherosclerotic lesions detectid by a monoclonal antibody" Active Oxygens,Lipid Peroxides,and Antioxidants. 139-148 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 高野 達哉: "nano GIGA(マクロファージの動脈硬化)" 日本臨牀社, 6 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 高野 達哉: "日本血管外科学会雑誌(動脈硬化発症における内皮機能)" 日本血管外科学会, 8 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] K.Magari,H.Fukushima,S.Ishimaru,et al.: "Platelet adhesion to a biomimetic prosthesis prepared from canine arterial wall." Artif.Organs. 15(6). 492-497 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] Y.Yagyu,R.Hashida,K.Iwasaki,et al.: "Effect of PGI_2 on platelet binding to partially denuded endothelial monolayer in vitro." Thromb.Res.64. 733-744 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] T.Imanaka,P.B.Lazarow,& T.Takano: "Suramin prevents import of acyl-CoA oxidase into rat liver peroxisomes." Biochim.Biophys.Acta. 1134. 197-202 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Y.Yagyu,C.Mineo,T.Imanaka,et al.: "Intercellular transport through a partially denuded arterial endothelial monolayer. Effect of platelets and PGI_2." Thromb.Res.66. 215-222 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] C.Mineo,T.Kanaseki,T.Imanaka,et al.: "Hydrolysis of lipid droplets in acid cholesteryl-esterase-deficient fibroblasts." Cell Struct.Funct.17. 191-196 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] T.Takano: "Accumulation of cholesteryl ester in atherosclerotic lesions." Acta Pathol.Jpn.42(9). 625-631 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 高野 達哉: "心臓(動脈硬化壁へのコレステロール蓄積機構)" 丸善株式会社, 8 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] 峰尾 千恵子,高野 達哉: "新生化学実験講座6(トランスサイトーシス)" 東京化学同人, 10 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] T.Imanaka,P.B.Lazarow and T.Takano: "A novel 57 kDa peroxisomal membrane polypeptide detected by monoclonal antibody (PXM1a/207B)." Biochim.Biophys.Acta. 1062. 264-270 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] K.Magari,H.Fukushima,S.Ishimaru,et al.: "Platelet adhesion to a biomimetic prosthesis prepared from canine arterial wall." Artifi.Organs. 15(6). 492-497 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Y.Yagyu,R.Hashida,K.Iwasaki,et al.: "Effect of PGI_2 on platelet binding to partially denuded endothelial monolayer in vitro." Thromb.Res.64. 733-744 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] T.Imanaka,P.B.Lazarow and T.Takano: "Suramin prevents import of acyl-CoA oxidase into rat liver peroxisomes." Biochim.Biophys.Acta. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Y.Yagyu,C.Mineo,T.Imanaka,et al.: "Intercellular transport through a partially denuded arterial endothelial monolayer.Effect of platelets and PGI_2." Thromb.Res.(1992)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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