Dynamics of shear-induced redistribution of F-actin in endothelial cells in vivo

Abstract

The steady-state responses of endothelial cell F-actin distribution to changes in in vivo shear stress have been well documented. The purpose of the current work was to define the dynamics of redistribution of F-actin in the period immediately after experimental changes in shear. We used abdominal aortic coarctation in rabbits to experimentally increase shear stress down-stream from the coarctation by approximately twofold. In situ staining was employed to track subsequent F-actin redistribution. Within 12-15 hours, the number of stress fibers in the central regions of the cells decreased, and some separation of junctional actin in adjacent cells occurred. Long, central stress fibers of variable thickness were evident at 24 hours, but the band of actin normally seen at the periphery of the cells could no longer be distinguished. The redistribution of F-actin was completed over the next 24 hours by an increase in thickness of central stress fibers. Restoration of normal F-actin distribution after coarctations were removed proceeded more slowly. The long, thick stress fibers that were induced by high shear were replaced by thinner or shorter microfilament bundles 48 hours after the coarctations were removed. At 72 hours, central stress fibers were primarily long, thin structures. Peripheral F-actin was not fully restored at this time. Peripheral F-actin was restored at 1 week after removal of the coarctation, but there were still more and longer stress fibers at this time than were observed in control aortas. If current hypotheses linking central stress fibers to cell-substrate adhesion and peripheral actin to permeability regulation are correct, then our data indicate that induction of high hemodynamic shear stress may transiently compromise substrate adhesion. Subsequent alterations may enhance substrate adhesion, although inter-cellular permeability may be altered due to reductions in peripheral actin.