IMMUNOSUPPRESSIVE AGENTS AND ENDOTHELIAL REPAIR - PREDNISOLONE DELAYSMIGRATION AND CYTOSKELETAL REARRANGEMENT IN WOUNDED PORCINE AORTIC MONOLAYERS

Endothelial denudation at areas of predilection to atherosclerosis is balanced by an active repair process that may be inhibited under condi tions of accelerated atherosclerosis. After cardiac transplantation, t he accelerated atherosclerotic process that develops may be enhanced b y immunosuppressive agents that have nonspecific effects on cell signa ling, proliferation, and response to injury. To study subtle effects o f cyclosporine A, azathioprine, and 6 alpha-methylprednisolone on norm al endothelial repair processes, confluent porcine endothelial monolay ers were denuded in the presence of clinically relevant concentrations of these agents. The rate of endothelial wound repair was compared an d the effects on cell spreading, proliferation, and the cytoskeleton a ssessed. 6 alpha-Methylprednisolone at concentrations of 1.25 to 50 mu mol/L was associated with a transient 30% to 60% inhibition of endoth elial wound repair. This was associated with increased cell size at th e wound edge and a delay in centrosomal reorientation toward the wound , without any effect on cell proliferation. Cyclosporine and azathiopr ine in clinically relevant concentrations did not affect endothelial r epair. Thus, corticosteroids transiently inhibit endothelial cytoskele tal alterations that are important in endothelial repair after a denud ing injury.