Takács E, Jellinek H
Int Angiol. 1987 Jan-Mar;6(1):7-19.
The theories and models concerning the pathology of arteriosclerosis are briefly reviewed. The Lipofundin arteriosclerosis model developed in our laboratory is present together with the mechanism of development of sclerotic vascular lesions and the primary role of permeability changes in the whole process. The process of development of the fibrotic proliferative lesions induced by Lipofundin was visualized by a colloidal iron tracer for enhanced permeability and the consequent smooth muscle cell proliferation was also registered. The presence and importance of adventitial lymphatic drainage was observed in connection with the enhancement of permeability. The adherence of macrophages to the endothelium was noted. We think that the enhanced permeability results in the functional impairment of the endothelium and causes macrophages to adhere to the damaged sites. Macrophages produce growth factors which together with enhanced permeability induce smooth muscle cell proliferation leading ultimately to the arteriosclerotic changes of the vessel wall. The pathological process was inhibited or at least attenuated by a prostacyclin-analog (Iloprost, 6-alpha-carbacyclin, Schering AG). The action of the drug seems to consist of a direct reduction of proliferation, of maintenance of normal permeability of normal endothelial functions. The latter acts against the adherence of macrophages thus cancels the possible stimulation of smooth muscle cell proliferation by macrophage growth factors.
本文简要回顾了有关动脉硬化病理学的理论和模型。介绍了我们实验室建立的脂褐素动脉硬化模型，以及硬化性血管病变的发展机制和通透性变化在整个过程中的主要作用。通过胶体铁示踪剂观察脂褐素诱导的纤维化增殖性病变的发展过程，发现通透性增强，随后平滑肌细胞增殖也得以记录。观察到外膜淋巴引流的存在及其重要性与通透性增强有关。注意到巨噬细胞与内皮细胞的黏附。我们认为，通透性增强导致内皮细胞功能受损，并使巨噬细胞黏附于受损部位。巨噬细胞产生生长因子，这些因子与通透性增强共同诱导平滑肌细胞增殖，最终导致血管壁的动脉硬化改变。一种前列环素类似物（伊洛前列素，6-α-卡前列素，先灵公司）可抑制或至少减轻这一病理过程。该药物的作用似乎包括直接减少增殖、维持正常内皮功能的正常通透性。后者可阻止巨噬细胞黏附，从而消除巨噬细胞生长因子对平滑肌细胞增殖的可能刺激。
