CIRCUMFERENTIAL DEFORMATION AND SHEAR-STRESS INDUCE DIFFERENTIAL RESPONSES IN SAPHENOUS-VEIN ENDOTHELIUM EXPOSED TO ARTERIAL FLOW

Adaptation of saphenous vein to the hemodynamic stresses of the arteri al circulation is critical to the maturation of vein bypass grafts, We have investigated early adaptive responses of venous endothelium by p lacing excised human saphenous vein in a bypass circuit with either ve nous or arterial flow conditions, using external stenting to resolve t he effects of longitudinal (shear) from circumferential stress. Endoth elial protein concentrations were assessed by immunostaining area (rat io of protein/CD31) and Western blotting of endothelial cell lysates ( staining ratio protein/vWf). In both unstented and stented veins nitri c oxide synthase increased after 90 min of arterial flow: twofold incr ease of immunostaining area (P = 0.001), four- to fivefold increase by Western blotting (P = 0.02), and increased A23187-mediated maximum en dothelium-dependent relaxation of vein rings (P = 0.01), In unstented veins, ICAM-1 concentration was increased after 45 min of arterial flo w: twofold increase by immunostaining (P = 0.001) and Western blotting (P = 0.038), with maximum fibrinogen-mediated endothelium-dependent r elaxation increasing from 55.9+/-4.9 to 97+/-2.1% (P = 0.01). In contr ast, in unstented veins there was a threefold decrease of VCAM-1 and n o change in P-selectin after arterial flow for 45 and 90 min, respecti vely, However, no changes in ICAM-1 and VCAM-1 were observed in stente d veins. The flow-induced alterations in nitric oxide synthase, ICAM-1 , and VCAM-1 were abolished when 3 mM tetraethylammonium ion (K+ chann el blocker) was included in the vein perfusate, The very rapid changes in ICAM-1 and VCAM-1 expression are a response to circumferential str ess, whereas the slower upregulation of nitric oxide synthase is a res ponse to longitudinal (shear) stress. Similar changes could influence the adhesiveness of endothelium in newly implanted saphenous vein bypa ss grafts.