Alterations in endothelial F-actin microfilaments in rabbit aorta in hypercholesterolemia

The current study tests whether hypercholesterolemia influences the distribution of endothelial cell microfilaments during the initiation and growth of fatty streak-type lesions. We classified the lesions occurring over a 20-week period into four types based on the location and extent of macrophage infiltration observed microscopically. The earliest lesion was characterized by leukocytes adherent to the endothelial surface. Minimal lesions were characterized by a few cells in the subendothelium. Intermediate lesions consisted of numerous subendothelial leukocytes in a minimally raised lesion. Advanced fatty streak lesions were elevated, with several layers of leukocytes. The organization of peripheral junctional actin (the dense peripheral band) and of central endothelial cell actin microfilament bundles was studied in each of these lesions by using fluorescent microscopy. We found that in the aorta away from branch sites and in areas away from lesions, the central microfilament distribution was unaffected by hypercholesterolemia. The macrophages entered the wall without any identifiable reorganization in the microfilaments. During the accumulation of subendothelial macrophages in minimal and intermediate lesions, stress fibers were initially increased in comparison to lesion-free areas. In raised advanced lesions, the central microfilaments became thinner and disappeared. However, at flow dividers, where central stress fibers are normally prominent, endothelial cells on the surface of intermediate lesions showed a reduction in central fibers, and peripheral bands became prominent. This finding was associated with changes in cell shape from elongated to cobblestone type. Thus, actin microfilament bundles in endothelial cells underwent substantial changes in distribution during the accumulation of subendothelial macrophages, forming hypercholesterolemia-induced fatty streak-type lesions. These changes may influence endothelial substrate adhesion, permeability, or repair after injury.