MECHANISMS OF ULTRASOUND-ENHANCED VASCULAR PERMEABILITY

Both continuous- and pulsed-wave ultrasound (US) have been shown to increase endothelial permeability to echogenic liposomes (ELIP) and stem cells associated with them in vitro and in vivo. We have been able to model this phenomenon in vitro with human umbilical vein endothelial cell (HUVEC) monolayers grown on transwell inserts. The US effect is not dependent on ELIP echogenicity, indicating that it is induced by radiation pressure, rather than by cavitation forces, and is blocked by N G -nitro-L-arginine methyl ester (L-NAME), an inhibitor of endothelial nitric oxide synthase (eNOS), establishing that it is mediated by nitric oxide (NO) signaling. Western blots of US-treated cultured HUVEC lysates and untreated controls indicated that NO activates the Akt pathway, implicating the intracellular transduction mechanism mediating shear stress effects on endothelial cells, but that other mechanoreceptor-triggered pathways may also be involved.