SHEAR-STRESS AND THE ENDOTHELIUM

Vascular endothelial cells (ECs) in vivo are influenced by two distinc t hemodynamic forces: cyclical strain due to vessel wall distention by transmural pressure, and shear stress, the frictional force generated by blood flow. Shear stress acts at the apical cell surface to deform cells in the direction of blood flow, wall distention tends to deform cells in all directions. The shear stress response differs, at least partly, from the cyclical strain response, suggesting that cytoskeleta l strain alone cannot explain it. Acute shear stress in vitro elicits rapid cytoskeletal remodeling and activates signaling cascades in ECs, with the consequent acute release of nitric oxide and prostacyclin; a ctivation of transcription factors nuclear factor (NF)kappa B, c-fos, c-jun and SP-1; and transcriptional activation of genes, including ICA M-1, MCP-1, tissue factor, platelet-derived growth factor-B (PDGF-B), transforming growth factor (TGF)-beta 1: cyclooxygenase-II, and endoth elial nitric oxide synthase (eNOS). This response thus shares similari ties with EC responses to inflammatory cytokines. In contrast, ECs ada pt to chronic shear stress by structural remodeling and flattening to minimize shear stress. Such cells become very adherent to their substr atum and show evidence of differentiation. Increased adhesion followin g chronic shear stress has been exploited to generate vascular grafts with confluent EC monolayers, retained after implantation in vivo: thu s overcoming a major obstacle to endothelialization of vascular prosth eses.