ADHESION AND DIFFERENTIATION OF ENDOTHELIAL-CELLS BY EXPOSURE TO CHRONIC SHEAR-STRESS - A VASCULAR GRAFT MODEL

Long-term patency of artificial vascular grafts for hemodialysis acces s and for bypass or interposition in small caliber arteries is limited due to neointimal hyperplasia and associated graft thrombosis. Given the anticoagulant and vasodilatory properties of endothelial cells, th ese problems could be partially overcome if grafts were seeded with an adherent monolayer of differentiated endothelial cells, prior to impl antation. Endothelial cells in vivo are highly adherent and can resist disruption by hemodynamic shear stress at levels that far exceed phys iological conditions. Endothelial cells in vivo also are highly differ entiated, with an organized cytoskeleton, Weibel-Palade bodies, and ba sal stress fibers with focal adhesion plaques. In cell culture, endoth elial cells rapidly lose many of their differentiated features, and en dothelial cells on artificial surfaces, like vascular graft material, are not sufficiently adherent or differentiated to resist physiologic shear stress. We find that endothelial cells exposed to chronic shear stress in vitro, applied in a stepwise fashion over several days, are induced to become tightly adherent to the substratum and exhibit more differentiated features. Thus, pre-conditioning of endothelial cells s eeded on vascular grafts with stepwise shear stress in vitro could be used to improve endothelial cell retention and differentiation for sub sequent in vivo use.