Injury and repair of endothelium at sites of flow disturbances near abdominal aortic coarctations in rabbits

Abstract

The acute and chronic effects of flow disturbances on arterial endothelium were studied by locally constricting the diameter of the rabbit abdominal aorta by 62% + 2.4% (mean ± SE). This procedure produced a region of elevated shear stress immediately upstream from the coarctation. A region of small irregular vortices was formed in the first 5 to 7 mm downstream, whereas an annular vortex was observed in the region from 2.0 to 2.5 cm further downstream. Morphologic changes to the endothelium near these coarctations were assessed by scanning electron microscopy; endothelial cell replication rates as a function of time after coarctation were monitored with 3H-thymidine. These studies established that profound alterations in endothelial cell shape caused by changes in local flow conditions immediately downstream from coarctations are primarily the result of alterations in morphology of pre-existing cells, rather than the proliferation of new cells with altered morphology. Definitive morphologic evidence of injury to endothelium was not seen at any sites after coarctation. Indeed, any early injury to endothelium caused by the flow disturbances was not sufficiently severe to cause a significant increase in endothelial cell turnover rate during the first week of coarctation. On the other hand, we observed a major increase in cell turnover (over 100-fold) by 30 days after coarctation at sites immediately upstream and immediately downstream of the coarctation. This finding suggests that flow-induced trauma can ultimately injure the cell sufficiently to cause cell death if the source of injury is persistent. Finally, we demonstrated that the high shear stress immediately upstream from the coarctation and the secondary flow disturbances immediately downstream can retard migration of endothelial cells into sites of injury, whereas repair was enhanced in the region of the primary annular vortex. These findings suggest that specific flow conditions, possibly characterized by relatively low and unidirectional shear forces, optimize migratory repair of endothelium. In conclusion, this study indicates that hemodynamic factors may influence the distribution of atherosclerotic lesions both by contributing to endothelial injury and by influencing endothelial repair.