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Role of parathyroid hormone-related peptide in vascular stenosis.

甲状旁腺激素相关肽在血管狭窄中的作用。

基本信息

批准号：
06670729
负责人：
SETO Shinji
金额：
$ 1.28万
依托单位：
Nagasaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

项目摘要

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.

血管平滑肌细胞（VSMC）的增殖被认为是血管成形术后再狭窄病理生理学的关键事件之一。据报道，甲状旁腺激素相关肽（PTHrP）及其受体是多种正常细胞类型中细胞生长的局部自分泌和旁分泌调节剂，位于 VSMC 附近。为了研究 PTHrP 如何参与球囊血管成形术后新内膜形成过程，我们检测了球囊裸露的大鼠颈动脉和通过定向斑块切除术回收的人冠状动脉中 PTHrP 的表达。在大鼠颈动脉中，RNase 保护测定和原位杂交表明，剥脱后 1 至 7 天，PTHrP mRNA 表达增加四至六倍，并持续 28 天，与 PTH/PTHrP 受体 mRNA 表达下调一致。原位杂交和免疫组织化学显示，球囊裸露的颈动脉中 PTHrP 表达主要位于新内膜。为了证实 PTHrP 参与人冠状动脉再狭窄病变，对人冠状动脉粥样斑块切除标本（23 个原发病变和 10 个再狭窄病变）进行了免疫组织化学分析。再狭窄标本中表达PTHrP蛋白的内膜细胞数量显着高于稳定型心绞痛或不稳定型心绞痛标本。这些数据表明，VSMC 中的 PTHrP 基因表达在新生内膜形成过程中显着增加，支持了以下假设：PTHrP 可能作为 VSMC 增殖的调节剂在血管狭窄中发挥重要作用。