| Project/Area Number |
06670729
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Nagasaki University |
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Principal Investigator |
SETO Shinji Assistant professor, The 3rd Department of Internal Medicine, Nagasaki University School of Medicine., 医学部, 講師 (00136657)
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| 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)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| 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)
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| Keywords | Parathyroid 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 |
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| 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.
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