The origin of foam cells in atherosclerosis.

The origin of the foam cells of experimental atherosclerotic lesions in rabbits has been investigated. Light and electron microscopic techniques were used. Lesions were induced by comparatively low elevations of serum cholesterol (up to 550 mg./100 ml.) and maintained in a narrow range (450-550 mg./100 ml.) by dietary manipulation. Two types of foam cell are described. One of these is considered to be a modified smooth muscle cell derived from the cells of the arterial media. The second is a macrophage of reticuloendothelial origin probably a blood monocyte. The smooth muscle foam cell is released into the developing plaque by destruction of the elastic laminae to which these cells are normally attached. Active migration of cells through intact or split laminae was not seen. Following assimilation of these cells into the plaque, modifications occur involving predominantly the cell ergastoplasm. Such modifications are considered to reflect activation of these cells to form collagen and elastic fibres in an attempt to regain their resting cell-fibre relationships and repair the damage to the arterial wall. The macrophage foam cell is an extremely active phagocyte which rapidly achieves large size and then degenerates. The cellular debris from this degeneration forms a considerable portion of the gruel core of older plaques. It is suggested that measures to promote the activities of the smooth muscle cell or to inhibit those of the macrophage could be of considerable importance in encouraging healing of atherosclerotic lesions and restoration of normal function to the damaged arterial wall.