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Role of parathyroid hormone-related peptide in vascular stenosis.

Research Project

Project/Area Number 06670729
Research Category

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

Allocation TypeSingle-year Grants
Research Field Circulatory organs internal medicine
Research InstitutionNagasaki University

Principal Investigator

SETO Shinji  Assistant professor, The 3rd Department of Internal Medicine, Nagasaki University School of Medicine., 医学部, 講師 (00136657)

Co-Investigator(Kenkyū-buntansha) OHTSURU Akira  Associate, Department of Cell Physiology, Atomic disease Institute, Nagasaki Uni, 医学部, 助手 (00233198)
YANO Katsusuke  Professor, The 3rd Department of Internal Medicine, Nagasaki University School o, 医学部, 教授 (50039864)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1995: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1994: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsParathyroid hormone-related peptide / Parathyroid hormone / parathyroid hormone-related peptide receptor / Restenosis / Atherectomy / Neointimal formation / PTCA後再狭窄 / 遺伝子治療 / 副甲状腺ホルモン関連ペプチド / 頚動脈バルーン障害モデル / RNase protection assay / in situ hybridization / アンチセンスオリゴヌクレオチ / HVJ-リポゾーム法 / PTHrP発現ベクター
Research Abstract

Proliferation of vascular smooth muscle cells (VSMCs) is considered to be one key event underlying the pathophysiology of restenosis after angioplasty. The parathyroid hormone-related peptide (PTHrP) and its receptor, a local autocrine and paracrine regulator of cellular growth in a variety of normal cell types, have been reported in the vicinity of VSMCs. To investigate how PTHrP might be involved in the process of neointimal formation after balloon angioplasty, we examined PTHrP expression in balloon-denuded rat carotid arteries and human coronary arteries that had been retrieved by directional atherectomy. In rat carotid arteries, the RNase protection assay and in situ hybridization demonstrated that PTHrP mRNA expression increased fourfold to sixfold 1 to 7 days after denudation and continued for 28 days, coincident with downregulation of PTH/PTHrP receptor mRNA expression. In situ hybridization and immunohistochemistry revealed that PTHrP expression in balloon-denuded carotid arteries was mainly localized to the neointima. To confirm the involvement of the PTHrP in human coronary artery restenotic lesions, immunohistochemical analysis of human coronary atherectomy specimens (23 primary and 10 restenotic lesions) was then performed. The number of intimal cells that expressed PTHrP protein was significantly higher in restenotic than in stable angina or unstable angina specimens. These data demonstrate that PTHrP gene expression in VSMCs markedly increases during neointimal formation, supporting the hypothesis that PTHrP may play an important role in vascular stenosis as a regulator of VSMC proliferation.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (5 results)

All Other

All Publications (5 results)

  • [Publications] Nakayama,T.,et al.: "Coronaly atherosclerotic smooth musle cells overexpress human parathyroid hormonerelated paptides." BIochem Biophys Res Commun. 200. 1028-1035 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Ozeki,S.,et al.: "Evidence that implicates the parathyroid hormonr-related peptide in vascular stenosis : Increased gene expression in the intima of injured rat carotid arteries and human restenotic colonary lesions." Arterioscler Thromb Vasc Biol. 16. 565-575 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Nakayama et al.: "Coronary atherosclerotic smooth muscle cells overexpress human parathyroid hormonerelated peptides." Biochem Biophys Res Commun. 200. 1028-1035 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] S.Ozeki et al.: "Evidence that implicates the parathyroid hormonerelated peptide in vascular stenosis : Increased gene expression in the intima of injured rat carotid arterise and human restenotic coronary lesions." Arterioscler Thromb Vasc Biol. 16. 565-575 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Ozeki S,Ohtsuru A,Seto S et al.: "Evidence that implicates the parathyroid hormone-related peptide in vascular stenosis : Increased gene expression in the intima of injured rat carotid arteries and human restenotic coronary lesions" Arterioscler Thromb Vasc Biol. 16(in press). (1996)

    • Related Report
      1995 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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