Enhanced endothelial permeability and invasion of leukocytes into the artery wall as initial events in experimental arteriosclerosis.

The temporal sequence of the very early events in arteriosclerosis, as induced by electrical stimulation in carotid arteries of rabbits, was examined by combined light microscopy and transmission electron microscopy. After one session (30 min) of DC impulses, the endothelial permeability to horse-radish peroxidase was increased mainly beneath the anode, judging from the massive accumulation of reaction products of peroxidase in the subendothelium. After a further stimulation period, some of the endothelial cells displayed alterations in pattern and size and heavy cytoplasmic deposition of silver salt. However, the endothelium was maintained as a continuous lining. During this initial phase, a considerable number of granulocytes and monocytes was found adhering to the endothelium of the stimulated region and also within the subendothelial space. The invasion of the leukocytes preceded the migration of smooth muscle cells from the media into the intima, a process which began after two days of the electrical stimulation schedule. These initial phases of plaque development may represent a special form of an inflammatory response.