ALTERATIONS IN ENDOTHELIAL F-ACTIN MICROFILAMENTS IN RABBIT AORTA IN HYPERCHOLESTEROLEMIA

The current study tests whether hypercholesterolemia influences the di stribution of endothelial cell microfilaments during the initiation an d growth of fatty streak-type lesions. We classified the lesions occur ring over a 20-week period into four types based on the location and e xtent of macrophage infiltration observed microscopically. The earlies t lesion was characterized by leukocytes adherent to the endothelial s urface. Minimal lesions were characterized by a few cells in the suben dothelium. Intermediate lesions consisted of numerous subendothelial l eukocytes in a minimally raised lesion. Advanced fatty streak lesions were elevated, with several lavers 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 t hese lesions by using fluorescent microscopy. We found that in the aor ta away from branch sites and in areas away from lesions, the central microfilament distribution was unaffected by hypercholesterolemia. The macrophages entered tile wall without any identifiable reorganization in the microfilaments. During the accumulation of subendothelial macr ophages in minimal and intermediate lesions, stress fibers were initia lly increased in comparison to lesion-free areas. In raised advanced l esions, the central microfilaments became thinner and disappeared. How ever, at flow dividers, where central stress fibers are normally promi nent, 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 fell share from elongated to cobblestone type. Thus, actin microfilament bundles in endothelial cells underwent substantial changes in distribution during the accumul ation of subendothelial macrophages, forming hypercholesterolemia-indu ced fatty streak-type lesions. These changes may influence endothelial substrate adhesion, permeability, or repair after injury.