Temporal sequence of morphological alterations in artery walls during experimental atherogenesis--occurrence of leukocytes.

In rabbit carotid arteries arteriosclerotic lesions were induced by repeated local transmural electrical stimulations. The sequence of early morphological alterations in the vessel wall and especially the kinetics of leukocytes were examined by transmission electron microscopy. After a stimulation period of only 1 day monocytes and heterophilic granulocytes adhered to the endothelial surface. In the subendothelium mainly beneath the anode, focal amorphous insudates were present together with mononuclear and granulocytic cells. Thereby, the endothelium was maintained as a continuous lining as shown by surface staining with silver nitrate. However, both pattern and size of the endothelial cells were altered in comparison to the controls. Some of the endothelial cells displayed a heavy cytoplasmic silver salt deposition. After 2 days of the electrical stimulation schedule, the first myocytes occurred in the subendothelial space. The mediamyocytes sending pseudopods through the internal elastic lamina still appeared to be in a contractile phenotype. In the 7-day-old proliferative lesion modulated smooth muscle cells were the predominant cell type; only 10%-20% of the subendothelial cells were identified as macrophages and heterophils. This proportion decreased further, and after a stimulation period of 28 days the granulocytes disappeared completely. At this stage of plaque development, the intimal myocyte population mainly consisted of contractile smooth muscle cells and intermediary states between the contractile and modulated phenotype. The insudation, immigration of white blood cells, and subsequent migration and proliferation of myocytes reinforces the view that the initial phases of arteriosclerotic lesions may represent a special form of an inflammatory response.