Role of macrophages and extracellular matrix in vascular remodeling

1.富含亮氨酸的小分子蛋白聚糖、核心蛋白聚糖和双糖蛋白聚糖可与TGF-β结合，被认为参与了动脉内膜增生中细胞外基质积聚的调节。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，我们分析了这些蛋白多糖和两种细胞因子在高胆固醇饮食（动脉粥样硬化组）和普通饮食（对照组）的家兔动脉粥样硬化支架植入后新生内膜形成过程中的空间和时间分布。我们将Gianturco的Z型支架植入兔髂动脉，并在第4-56天收获髂动脉进行免疫组织化学和原位杂交分析。结果提示，尽管双糖链蛋白聚糖和核心蛋白聚糖的结构相似，但它们在动脉损伤后新生内膜形成过程中的动力学过程却截然不同;双糖链蛋白聚糖的合成与胚胎平滑肌细胞有关，而核心蛋白聚糖的合成在血管损伤后晚期被巨噬细胞分泌的IL-1 β所加速。为了阐明这种多样性的血管病变的机制，我们用化学方法检测了易卒中的自发性高血压大鼠的高血压血管病变，并参考了巨噬细胞亚群的分布。结果提示，巨噬细胞浸润时间及巨噬细胞亚群在各器官血管中分布的不均一性与高血压血管病变的多样性有关。巨噬细胞的供应途径及其功能的差异可能决定了血管病变的病理变化。

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.