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Role of macrophages and extracellular matrix in vascular remodeling

巨噬细胞和细胞外基质在血管重塑中的作用

基本信息

批准号：
08670795
负责人：
MASUDA Junichi
金额：
$ 1.41万
依托单位：
Shimane Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

1.Leucine-rich small proteoglycans, decorin and biglycan, which can bind to TGF-beta, are considered to participate in regulation of extracellular matrix accumulation in arterial intimal hyperplasia. To investigate their correlation with the cellular localization and phenotypic modulation of smooth muscle cells, we analyzed the spatial and chronological distribution of these proteoglycans and two cytokines in the process of neointima formation after stent implantation in aortas of rabbits fed on both high-cholesterol chow (atherosclerotic group) and regular one (control group). We implanted Gianturco's Z type stents in the rabbit aortas and harvested the aortas at day 4-56 days for immunohistochemical and in situ hybridization analysis. The results supprted that the biglycan and decorin kinetics during neointima formation after arterial injury are distinct in spite of their similar construction ; biglycan synthesis correlates with the embryonic smooth muscle cells, whereas decorin synthesis is accelerated by IL-1betasecreted from macrophages accumulating in the injured areas in the late stage after the vascular injury.2.In hypertensive vascular lesions, various pathologic changes are exhibited. To clarify the mechanisms responsible for this diversity of vascular lesions, we immunohistochemically examined hypertensive vascular lesions in stroke-prone spontaneously hypertensive rats with reference to the distribution of macrophage subsets. The results suggest that heterogeneity in the time course of macrophage infiltration and inthe distribution of macrophage subsets among the vascular tres of various organs seems to be correlated with the diversity of hypertensive vascular lesions. Differences in the routes that supply macrophages and their functions may determine the pathologic changes in the vascular lesions.

1.富含亮氨酸的小蛋白聚糖、decorin和biglycan可与tgf - β结合，被认为参与了动脉内膜增生中细胞外基质积累的调控。为了研究它们与平滑肌细胞的细胞定位和表型调节的相关性，我们分析了高胆固醇食物（动脉粥样硬化组）和正常食物（对照组）在主动脉支架植入后新内膜形成过程中这两种蛋白多糖和两种细胞因子的空间和时间分布。我们在兔主动脉内植入Gianturco’s Z型支架，并于第4-56天采集主动脉进行免疫组化和原位杂交分析。结果表明，尽管结构相似，但在动脉损伤后新内膜形成过程中，biglycan和decorin的动力学是不同的；大聚糖的合成与胚胎平滑肌细胞相关，而血管损伤后期巨噬细胞分泌的il -1 β加速了decorin的合成。高血压血管病变表现为多种病理改变。为了阐明这种血管病变多样性的机制，我们参考巨噬细胞亚群的分布，用免疫组织化学方法检查了卒中易发自发性高血压大鼠的高血压血管病变。结果提示，巨噬细胞浸润时间和各器官血管中巨噬细胞亚群分布的异质性似乎与高血压血管病变的多样性有关。巨噬细胞供给途径及其功能的差异可能决定了血管病变的病理变化。