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治疗后新生内膜增厚的主要原因。猪冠状动脉球囊损伤后两周植入冠状动脉支架。随时间推移观察支架植入部位，并检测蛋白激酶C（PKC）的表达。支架植入后 3 天观察到新形成的新内膜，7 天后管腔狭窄明显。支架支柱周围有浸润性巨噬细胞。在增殖的新内膜中观察到 PKC 的阳性免疫反应性。我们的数据表明PKC对支架植入后平滑肌细胞增殖的影响。2．据报道，血管内皮生长因子（VEGF）可诱导新内膜增殖。猪冠状动脉球囊损伤后2周植入冠状动脉支架，时程观察VEGF和fit-1的表达。支架植入后第7天和第1天、第4天新生内膜中可见VEGF和fit-1的表达。在支架支柱周围观察到强免疫反应性，28天时巨噬细胞浸润。第1天、第4天和第28天内皮细胞出现阳性免疫反应。 VEGF不仅显示了内皮细胞增殖的作用，还通过fit-1.3显示了VSMC增殖的作用。据报道，Rho激酶（Rho K）参与冠状动脉介入治疗后VSMC的增殖。猪冠状动脉球囊损伤两周后，通过药物输送导管施用 Rho K 抑制剂 Y27632。 4周后收获递送位点，并检查Rho K的表达。超声检查显示，Y27632组新内膜增殖受到抑制，管腔保持更宽。免疫组化结果显示Y27632组Rho K表达减少。 Rho k 抑制剂可能成为预防再狭窄、抑制新内膜增殖的有用工具。