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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:1166-1171.)
© 1995 American Heart Association, Inc.

Articles

Immunosuppressive Agents and Endothelial Repair

Prednisolone Delays Migration and Cytoskeletal Rearrangement in Wounded Porcine Aortic Monolayers

Presented in part at the Xth Scientific Sessions of the American College of Cardiology, Dallas, Tex, March 6-9, 1992, and published in abstract form in J Am Coll Cardiol. 1992;19:121A.

Alistair I. Fyfe; Alan Rosenthal; Avrum I. Gotlieb

From the Vascular Research Laboratory, Department of Pathology, and The Banting and Best Diabetes Center, University of Toronto, and The Toronto Hospital, Toronto, Ontario, Canada (A.R., A.I.G.), and the UCLA Division of Cardiology, Los Angeles, Calif (A.I.F.).

Correspondence to Alistair I. Fyfe, UCLA Division of Cardiology, 47-123 CHS, 10833 Le Conte Ave, Los Angeles, CA 90024-1679. E-mail afyfe@medicine.medsch.ucla.edu.

Abstract Endothelial denudation at areas of predilection to atherosclerosis is balanced by an active repair process that may be inhibited under conditions of accelerated atherosclerosis. After cardiac transplantation, the accelerated atherosclerotic process that develops may be enhanced by immunosuppressive agents that have nonspecific effects on cell signaling, proliferation, and response to injury. To study subtle effects of cyclosporine A, azathioprine, and 6-methylprednisolone on normal endothelial repair processes, confluent porcine endothelial monolayers were denuded in the presence of clinically relevant concentrations of these agents. The rate of endothelial wound repair was compared and the effects on cell spreading, proliferation, and the cytoskeleton assessed. 6-Methylprednisolone at concentrations of 1.25 to 50 µmol/L was associated with a transient 30% to 60% inhibition of endothelial wound repair. This was associated with increased cell size at the wound edge and a delay in centrosomal reorientation toward the wound, without any effect on cell proliferation. Cyclosporine and azathioprine in clinically relevant concentrations did not affect endothelial repair. Thus, corticosteroids transiently inhibit endothelial cytoskeletal alterations that are important in endothelial repair after a denuding injury.

Key Words: cyclosporine A • wound repair • azathioprine • endothelium • corticosteroids

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