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Immunohistochemical and molecular biological studies of vascular smooth muscle cell proliferation after coronary stent implantation

冠状动脉支架植入后血管平滑肌细胞增殖的免疫组织化学和分子生物学研究

基本信息

批准号：
11670708
负责人：
KATAGIRI Takashi
金额：
$ 2.18万
依托单位：
Showa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670708/
关键词：
Stent Restenosis Vascular smooth muscle cell Endothelial cell Coronary intervention Rho kinase VEGF PK C

项目摘要

1. Proliferation of vascular smooth muscle cells is the main cause of neointimal thickening after coronary intervention. Coronary stents were implanted 2 weeks after balloon injury of porcine coronary arteries. Stent implanted sites were observed in time-course, and the expression of protein kinase C (PKC) were examined. Newly formed neointima was observed 3 days after stenting and the luminal narrowing was prominent from 7 days. There were infiltrating macrophages around stent struts. Positive immunoreactivities of PKC were seen in the proliferated neointima. Our data suggests that the imvolvement of PKC on the smooth muscle cell proliferation after stent implantation.2. It is reported that vascular endothelial growth factor (VEGF) induces neointimai proliferation. Coronary stents were implanted 2 weeks after balloon injury of porcine coronary arteries, and the expressions of VEGF and fit-1 were observed in time-course. The expressions of VEGF and fit-1 were found in the neointima 7 and 1 4 days after stenting. Strong immunoreactivities were observed around stent strut which macrohpages were infiltrated at 28 days. There were positive immunoreactivities in the endothelial cells 1 4 and 28 days. VEGF shows not only the effect of endothelial cell proliferation but also the effect of VSMC proliferation through fit-1.3. It is reported that Rho kinase (Rho K) is involved in the proliferation of VSMC after coronary intervention. Two weeks after balloon injury of porcine coronary arteries, Y27632, which is an inhibitor of Rho K, was administered through drug delivery catheter. The delivery sites were harvested after 4 weeks, and the expression of Rho K was examined. In ultrasound, neointimai proliferation was inhibited, and the lumen was kept wider in Y27632 group. The expression of Rho K was diminished in immnohistochmistry in Y27632 group. Rho k inhibitor may become a useful tool to prevent restenosis inhibiting neointimal proliferation.

1.血管平滑肌细胞增殖是冠状动脉介入术后新生内膜增厚的主要原因。在猪冠状动脉球囊损伤后2周植入冠状动脉支架。动态观察支架植入部位，并检测支架植入后蛋白激酶C（PKC）的表达。支架植入后3天观察到新生内膜，从7天开始管腔狭窄明显。支架支柱周围有浸润性巨噬细胞。增生的新生内膜中可见PKC免疫反应阳性。提示PKC参与了支架置入后平滑肌细胞的增殖.血管内皮生长因子（VEGF）可诱导新生内膜增殖。球囊损伤猪冠状动脉2周后植入支架，观察血管内皮生长因子（VEGF）和fit-1的表达。支架术后第7天和第1 ~ 4天新生内膜VEGF和fit-1表达。第28天，支架支柱周围可见强免疫反应，巨噬细胞浸润。内皮细胞免疫反应阳性反应在14和28天。VEGF不仅具有促内皮细胞增殖的作用，而且通过fit-1也具有促VSMC增殖的作用。有研究表明Rho激酶（Rho K）参与了冠状动脉介入术后血管平滑肌细胞的增殖。在猪冠状动脉球囊损伤后两周，通过药物递送导管施用Rho K抑制剂Y27632。4周后收集分娩部位，并检查Rho K的表达。超声下，Y27632组新生内膜增生受到抑制，管腔保持较宽。免疫组化显示Y27632组Rho K表达减弱。Rho k抑制剂可能成为预防再狭窄的有效工具，抑制新生内膜增殖。