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New therapy against myocardial infarction using synthetic peptides

Research Project

Project/Area Number 02557038
Research Category

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

Allocation TypeSingle-year Grants
Research Field Circulatory organs internal medicine
Research InstitutionUniversity of Tokyo

Principal Investigator

YAZAKI Yoshio  University of Tokyo, Faculty of Medicine, professor, 医学部(病), 教授 (20101090)

Co-Investigator(Kenkyū-buntansha) KATOH Hirohisa  Yamasa Co.Ltd., Research and Development Division, Staff, 研究開発部・生物第2研究室, 研究員
SUGI Masato  Yamasa Co.Ltd., Research and Development Division, Senior Staff, 研究開発部・生物第2研究室, 主任
YAMAZAKI Tsutomu  University of Tokyo, Faculty of Medicine, Assistant, 医学部(病), 助手
SEKO Yoshinori  University of Tokyo, Faculty of Medicine, Assistant, 医学部(病), 助手
YAMAOKI Kazuhide  University of Tokyo, Health Administration Center for Students, Assistant Profes, 保健センター, 講師 (70182409)
栗原 裕基  東京大学, 医学部(病), 助手
Project Period (FY) 1990 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥10,800,000 (Direct Cost: ¥10,800,000)
Fiscal Year 1992: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1991: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1990: ¥6,600,000 (Direct Cost: ¥6,600,000)
KeywordsRGD / Acute Myocardial Infarction / Myocardial Reperfusion Injury / Cell Adhesion Molecules / Antibody treatment / CD11a, b, c / 心筋虚血再潅流 / DD11a,b,c / CD54(ICAM-1) / CD62(GMP-140) / CD11a,b,c / CD54(ICAMー1) / CD18
Research Abstract

The migration of neutrophils into tissues is the central event in myocardial hypoxiareoxygenation (H/R) as well as in inflammatory responses. The rolling of neutrophils has been revealed to be the first step of the interaction of the neutrophils with the vessel wall during an inflammatory response, which is dependent of the expression of granule membrane protein-140 (GMP-140) on the surface of vascular endothelial cells. First, using an in vitro model of H/R,we showed that higher number of neutrophils adhered to human umbilical vein endothelial cells (HUVECs) subjected to 60 minutes of hypoxia followed by 30 minutes of reoxygenation compared with neutrophils adhered to HUVECs subjected to no stimulation of I/R,and that preincubation of HUVECs with anti-human GMP-140 antibody blocked these adhesion. Furthermore, immunoperoxidase staining clarified, for the first time, that H/R enhanced the expression of GMP-140 on the surface of HUVECs. Next, using an in vivo rat model of myocardial ischemiareperfusion (I/R), we indicated that within 2 hours after reperfusion leukocytes began to infiltrate into the rat myocardia subjected to 30 minutes of ischemia, and clarified, for the first time, that the expression of intercellular adhesion molecule-1 (ICAM-1) was enhanced on the capillary and venous endothelial cells from 8 to 96 hours after the start of reperfusion. Furthermore, pretreatment with individual monoclonal antibodies against cell-adhesion molecules (CD11a, CD11b+c, CD18 and ICAM-1) reduced not only the infiltration of leukocytes but also the area of infarction in the reperfused hearts. Our present study suggests that the expression of GMP-140 along with ICAM-1 on vascular endothelial cells play a critical role in myocardial injury induced by I/R.

Report

(4 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • 1990 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] I.Komuro,Y.Katoh,T.Kaida,Y.Shibazaki,M.Kurabayashi,E.Hoh,F.Takaku,Y.Yazaki: "Mechanical loading stimulates cell hypertrophy and specific gene expression in cultured rat cardiac myocytes ; possible role of protein kinase C activation." J.Biol.Chem.266. 1265-1268 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] M.Kuro-o,R.Nagai,K.Nakahara,H.Katoh,R.Tsai,H.Tsuchimochi,Y.Yazaki,A.Ohkubo,F.Takaku: "cDNA cloning of a myosin heavy chain isoform in embryonic smooth muscle and its expression during vascular development and in arteriosclerosis." J.Biol.Chemist.266. 3768-3773 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Y.Seko.Y.Shinkai,A.Kawasaki,H.Yagita,K.Okumura,F.Takaku,Y.Yazaki: "Expression of perforin in infiltrating cells in murine hearts with acute myocarditis caused by coxsackievirus B3." Circulation. 84. 788-795 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] I.Komuro,Y.Katoh,E.Hoh,F.Takaku,Y.Yazaki: "Mechanisms of cardiac hypertrophy and injury-possible role of protein kinase-C activation." Jpn.Circ.J.55. 1149-1157 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] T.Yamazaki,K.Tobe,E.Hoh,K.Maemura,T.Kaida,I.Komuro,H.Tamemoto,T.Kadowaki,R.Nagai,Y.Yazaki: "Mechanical loading activates mitogen-acitvated protein kinase and S6 peptide kinase in cultured rat cardiac myocytes." J.Biol.Chem.268. 12069-12076 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] T.Yamazaki,Y.Seko,T.Tamatani,M.Miyasaka,H.Yagita,K.Okumura,R.Nagai,Y.Yazaki: "Expression of intercellular adhesion molecule-I in rat heart with ischemia/reperfusion and limitation of infarct size by treatment with antibodies against cell adhesion molecules." Am.J.Pathology. 143. 410-418 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Y.Yazaki,M.Kurabayashi,I.Komuro: "Recent Progress in Failing Heart Syndrome" Springer-Verlag Tokyo., 344 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Y.Yazaki,I.Komuro.: "Cardiomyopathy Update 4 Metabolic and Molecular Aspects of Cardiomyopathy" University of Tokyo Press, 366 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] I.Komuro, Y.Katoh, T.Kaida, Y.Shibazaki, M.Kurabayashi, E.Hoh, F.Takaku, Y.Yazaki: "Mechanical loading stimulates cell hypertrophy and specific gene expression in cultured rat cardiac myocytes : possible role of protein kinase C activation" J.Biol.Chem.266 (2). 1265-1268 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] M.Kuro-o, R.Nagai, K.Nakahara, H.Katoh, R.Tsai, H.Tsuchimochi, Y.Yazaki, A.Ohkubo, F.Takaku: "cDNA cloning of a myosin heavy chain isoform in embryonic smooth muscle and its expression during vascular development and in arteriosclerosis." J.Biol.Chemist.266 (6). 3768-3773 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Y.Seko, Y.Shinkai, A.Kawasaki, H.Yagita, K.Okumura, F.Takaku, Y.Yazaki: "Expression of perforin in infiltrating cells in murine hearts with acute myocarditis caused by coxsackievirus B3" Circulation. 84 (2). 788-795 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] I.Komuro, Y.Katoh, E.Hoh, F.Takaku, Y.Yazaki: "Mechanisms of cardiac hypertrophy and injury-possible role of protein kinase-C activation" Jpn.Circ.J.55 (11). 1149-1157 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] T.Yamazaki, K.Tobe, E.Hoh, K.Maemura, T.Kaida, I.Komuro, H.Tamemoto, T.Kadowaki, R.Nagai, Y.Yazaki: "Mechanical loading activates mitogen-activated protein kinase and S6 peptide kinase in cultured rat cardiac myocytes." J.Biol.Chem.268 (16). 12069-12076 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] T.Yamazaki, Y.Seko, T.Tamatani, M.Miyasaka, H.Yagita, K.Okumura, R.Nagai, Y.Yazaki: "Expression of intercellular adhesion molecule-1 in rat heart with ischemia/reperfusion and limitation of infarct size by treatment with antibodies against cell adhesion molecules." Am.J.Pathology. 143 (2). 410-418 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Y.Yazaki, M.Kurabayashi, I.Komuro: Molecular basis for cardiac adaptation to overload. in "Recent Progress in Failing Heart Syndrome" ed by S.Sasayama, H.Suga. Springer-Verlag Tokyo, 19-41 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Y.Yazaki, I.Komuro: Molecular analysis of cardiac hypertrophy due to mechanical stress.in "Cardiomyopathy Update 4 Metabolic and Molecular Aspects of Cardiomyopathy" ed by L.H.Opie and T.Sugimoto. University of Tokyo Press, 35-43 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] I,Komuro,etc: "Stretching of cardiac mycytes stimulates protooncogene expression." J.Biol.Chem.265(7). 3595-3598 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] I.Komuro,etc: "Molecular cloning of gene sequences from rat heart rapidly responsive to pressure overload." Circ.Res.66(4). 979-985 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Y.katoh,etc: "Messenger RNA lavels of guanine nucleotideーbinding proteins are reduced in the ventricle of cardiomyopathic hamsters." Circ.Res.67(1). 235-239 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] T.Sugiyama,etc: "Cytoplasmic calcium ion elevating factor(s) in spontaneously hypertensive rat serum." J.Hypertension. 8(10). 919-925 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Y.Seko,etc: "Expression of major histocompatibility complex class I antigen in murine ventricular myocytes infected with coxsackievirus B3." Chirc.Res.67(2). 360-367 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] M.kurabayashi,etc: "Functional identification of the transcriptional regulatory elements within the promoter region of the human ventricular myosin alkali light chain gene." J.Biol.Chem.265(31). 19271-19278 (1990)

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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