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2003 Fiscal Year Final Research Report Summary

ROLE OF MAPKinases ON MOLECULAR MECHANISUMS OF CARDIOVASCULAR REMODELING

Research Project

Project/Area Number 14370036
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionOSAKA CITY UNIVERSITY

Principal Investigator

IWAO Hiroshi  OSAKA CITY UNIVERSITY MEDICAL SCHOOL, PHARMACOLOGY, PROFESSOR, 大学院・医学研究科, 教授 (00137192)

Co-Investigator(Kenkyū-buntansha) MITSUYAMA Shokei  KUMAMOTO UNIVERSITY MEDICAL SCHOOL, PHARMACOLOGY, PROFESSOR, 大学院・医学薬学研究科, 教授 (10195414)
Project Period (FY) 2002 – 2003
KeywordsRENIN-ANGIOTENSIN SYSTEM / SIGNAL TRANSDUCTION / ORGAN DAMAGE / MAP KINASE / CARDIAC HYPERTROPHY / ANGIOTENSIN RECEPTOR ANTAGONIST / APOPTOSIS SIGNAL-REGULATING KINASE 1 / Thy-1 NEPHRITIS
Research Abstract

The renin-angiotensin-aldosterone system (RAAS) plays an important role in both the physiological regulation of blood pressure and in the pathophysiological disruption of cardiovascular organ damages. Angiotensin II (Ang II) is the primary biological mediator of the RAAS. Pathophysiological actions of Ang II is mediated by the angiotensin II type I receptor, for examples of, vasoconstriction on vascular smooth muscle, secretion of aldosterone, reabsorption of sodium in the renal proximal nephron, and cell growth and proliferation.
Treatments of RAAS inhibitors, angiotensin converting enzyme and Ang II type I receptor antagonist, in hypertensive rat models caused prevention effects of hypertension, cardiac hypertrophy, and vascular sclerosis and glomerular sclerosis. In addition, these effects were associated with suppressive gene expressions of TGF-b, collagen type I, collagen type II, fibronectin. These gene expressions were caused by the stimulation of Ang II type I receptor through the activation of mitogen activated protein kinases (ERK and JNK). Both angiotensin converting enzyme and Ang II type I receptor antagonist inhibited the activation of ERK and JNK.
In this study, we investigated the role of apoptosis signal-regulating kinase 1 (ASK-1),ERK,JNK,p38 and activated protein 1 (AR 1) on cardiovascular organ damages. Furthermore, transcriptome analysis of glomerulus was performed in Thy-1 glomerular nephritis model. ASK-1,ERK,JNK,p38 and AP-1 are crossly related to the cardiac hypertrophy, vascular neointimal hyperplasia and glomerular damages. These results suggested that MAP Kinases family is proposed to be a potential therapeutic target for cardiovascular diseases.

  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Yamada Mら他7名: "Molecular mechanism and role of endothelial monocyte chemoattractant oritein-1 induction by vascular endothelial growth factor."Artherioscler Thromb Vase Biol. 23. 1996-2001 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Izumiya Yら他7名: "Apoptosis signal-regulating kinase 1 plays a pivotal role in angiotensin-II-induced cardiac hypertrophy and remodeling."Circulation Research. 93. 874-883 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Izumi Yら他10名: "Activation of apoptosis signal-regulating kinase 1 in injured artery and its critical role in neointimal hyperplasia."Circulation. 108. 2812-2818 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Zhan Yら他6名: "Role of JNK, p38, and ERK in platelet-derived growth factor-induced vascular proliferation, migration, and gene expression."Arterioscular Thromb Vase Biol. 23. 795-801 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kim S, Iwao H: "Stress and vascular responses : mitogen-activated protein kinases and activator protein-1 as promising therapeutic targets of vascular remodeling."Journal of Pharmacological Sciences. 91. 177-181 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Zhan, Y., Kim, s., Yasumoto, H., Namba, M., Miyazaki H., Iwao, H.: "Effects of Dominant-Negative c-Jun on Platelet-Derived Growth Factor-Induced Vascular Smooth Muscle Cell Proliferation"Arterioscler.Thromb.Vasc.Biol.. 22. 82-88 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Taniguchi, M., Kim, S., Zhan, Y., Iwao, H.: "Role of intrarenal angiotensin-converting enzyme in nephropathy of type II diabetic rats"Hypertension Res.. 25. 287-294 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Zhan, Y., Kim, S., Kwano, H., Iwao, H.: "Enhancement of glomerular platelet-derived growth factor beta-receptor tyrosine phosphorylation in hypertensive rats and its inhibition by calcium channel blocker"Hypertension Re.. 25. 295-301 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kim, S., Izumi, Y., Izumiya, Y., Zhan, Y., taniguchi, M., Iwao, H.: "Beneficial Effects of Combined Blockade of ACE and AT 1 Receptor on Intimal Hyperplasia in Balloon-Injured Rat Artery"Arterioscler.Thromb.Vasc.Biol.. 22. 1299-1304 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kim, S., Iwao, H.: "Stress and vascular responses: mitogen-activated protein kinases and AT1 as promising therapeutic targets of vascular remodeling"J.Pharmacol.Sci.. 91. 177-181 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Zhan, Y., Kim, S., Izumi, Y., Izumiya, Y., Nako, T., Miyazaki, H., Iwao, H.: "Role of JNK, p38, and ERK in Platelet-Derived Growth Factor-Induce Vascular Proliferation, Migration, and Gene Expression"Arterioscler.Thromb.Vasc.Biol.. 23. 795-801 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Izumiya, Y., Kim, S., Izumi, Y., Yoshida, K., Yoshiyama, M., Matsuzawa, A., Ichijo, H., Iwao, H.: "Apoptosis signal-regulating kinase 1 plays a pivotal role in angiotensin II-induced cardiac hypertrophy and remodeling"Circ.Res.. 93. 874-883 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Izumi, Y., Kim, S., Yoshiyama, M., Izumiya, Y., Yoshide, K., Koyama, H., Nishizawa, Y., Ichijo, H., Yoshikawa, J., iwao, H.: "Activation of Apoptosis Signal-Regulating Kinase 1 in Injured Artery and Its Critical Role in Neointimal Hyperplasia"Circulation. 108. 2812-2818 (2003)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2005-04-19  

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