Early morphological changes of vessels in an experimental model system.

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.