EXPERIMENTAL STUDIES ON ARTERIAL LESIONS

III.AUTORADIOGRAPHIC STUDIES ON THE MORPHOGENESIS OF ARTERIOSCLEROSIS USING THYMIDINE-H³

Abstract

1. Fibrocellular intimal thickening was produced in the left carotid arteries of rats by single ligations of them. At 2 days10weeks after the ligations, the animals were intravenously injected with thymidine-H³ and sacrificed 3 hours after the injections. And labeled and radioactive cells (proliferating cells) were autoradiographically investigated.
At 2 days after the ligation, intimal cells were not yet observed, but endothelial cells were remarkably proliferated (radioactive index, RI, i. e. % labeled cells : 6.1). At 4 and 8 days after the ligation, one to several layers of intimal cells appeared. Endothelial cells of the arteries were considerably proliferated (RI : 3.1), and the intimal cells were more conspicuously proliferated (RI : 7.5). At 5 and 10 weeks after the ligation, radioactive index of endothelial cells was 1.7, and that of intimal cells 0.6. At 2 days10 weeks after the ligation, smooth muscle cells of the media showed scarcely any proliferation (RI : 0.1). In normal control arteries, there was scarcely any proliferation of endothelial cells and medial smooth muscle cells (RI : 0.14 and 0.08).
From these results, the intimal cells are assumed to be derived from endothelial cells.
2. Thrombi formed in the vicinitiy of the ligation were investigated with the aforementioned method. The autoradiographical findings suggested that most of fibroblasts organizing the thrombi were considered to be derived from the arterial endothelial cells in the neighborhood of the formed thrombi.
3. The so-called atherosclerosis was formed in the thoracic aorta of rabbits by feeding a diet containing 1% cholesterol and 5% lard for 4-24 weeks. Slices of the aorta with lesions were incubated for 3 hours (37°C) in thymidine-H³-added whole blood or thymidine-H³-added blood plasma from these animals, and labeled cells (proliferating cells) were autoradiographically investigated.
In the animals fed with cholesterol for 4 or 7 weeks, endothelial cells and intimal cells were proliferated, but there were no radioactive cells in the media. At 13 or 24 weeks feeding, endothelial cells and cells of the superficial layer of the intimal (fibrocellular cap) were proliferated, but not in the medial cells.
In normal control rabbits, scarcely any proliferation was observed in endothelial cells and in the medial smooth muscle cells.
It has thus found that in the formation of mass of foam cells, endothelial cells and cells of the superficial layer of the intima are proliferated. Accordingly it was assumed that most of foam cells are derived from endothelial and intimal cells.