Adaptation of saphenous vein to the hemodynamic stresses of the arterial circulation is critical to the maturation of vein bypass grafts. We have investigated early adaptive responses of venous endothelium by placing excised human saphenous vein in a bypass circuit with either venous or arterial flow conditions, using external stenting to resolve the effects of longitudinal (shear) from circumferential stress. Endothelial protein concentrations were assessed by immunostaining area (ratio of protein/CD31) and Western blotting of endothelial cell lysates (staining ratio protein/vWf).In both unstented and stented veins nitric oxide synthase increased after 90 min of arterial flow: twofold increase of immunostaining area ( P ϭ 0.001), four-to fivefold increase by Western blotting ( P ϭ 0.02), and increased A23187-mediated maximum endothelium-dependent relaxation of vein rings ( P ϭ 0.01). In unstented veins, ICAM-1 concentration was increased after 45 min of arterial flow: twofold increase by immunostaining ( P ϭ 0.001) and Western blotting ( P ϭ 0.038), with maximum fibrinogen-mediated endothelium-dependent relaxation increasing from 55.9 Ϯ 4.9 to 97 Ϯ 2.1% ( P ϭ 0.01). In contrast, in unstented veins there was a threefold decrease of VCAM-1 and no change in P-selectin after arterial flow for 45 and 90 min, respectively. However, no changes in ICAM-1 and VCAM-1 were observed in stented veins. The flow-induced alterations in nitric oxide synthase, ICAM-1, and VCAM-1 were abolished when 3 mM tetraethylammonium ion (K ϩ channel blocker) was included in the vein perfusate.The very rapid changes in ICAM-1 and VCAM-1 expression are a response to circumferential stress, whereas the slower upregulation of nitric oxide synthase is a response to longitudinal (shear) stress. Similar changes could influence the adhesiveness of endothelium in newly implanted saphenous vein bypass grafts. ( J. Clin. Invest. 1997. 99:2719-2726.)

Abstract-It has been reported that fibrinogen may act as a bridging ligand, binding to intercellular adhesion molecule-1 (ICAM-1) on human umbilical vein endothelial cells and to Mac-1 on THP-1 cells (a monocytic cell line) to increase adhesion. In this study, we investigated whether fibrinogen altered the expression of ICAM-1 and, thus, increased the adhesion of THP-1 cells to cultured human saphenous vein endothelial cells (

Whole-cell patch-clamp electrophysiological investigation of endothelial cells cultured from human saphenous vein (HSVECs) has identified a voltage-gated Na ؉ current with a mean peak magnitude of ؊595 ؎ 49 pA (n ‫؍‬ 75). This current was inhibited by tetrodotoxin (TTX) in a concentration-dependent manner, with an IC 50 value of 4.7 M, suggesting that it was of the TTXresistant subtype. An antibody directed against the highly conserved intracellular linker region between domains III and IV of known Na ؉ channel ␣-subunits was able to retard current inactivation when applied intracellularly. This antibody identified a 245-kDa protein from membrane lysates on Western blotting and positively immunolabeled both cultured HSVECs and intact venous endothelium. HSVECs were also shown by reverse transcription-polymerase chain reaction to contain transcripts of the hH1 sodium channel gene. The expression of Na ؉ channels by HSVECs was shown using electrophysiology and cell-based enzyme-linked immunosorbent assay to be dependent on the concentration and source of human serum. Together, these results suggest that TTX-resistant Na ؉ channels of the hH1 isoform are expressed in human saphenous vein endothelium and that the presence of these channels is controlled by a serum factor. Vascular endothelial cells form the primary interface between the blood and the underlying tissue. These cells not only provide a barrier of varying permeability between the blood and the smooth muscle of the vessel wall, but are a major contributor to the processes of vascular growth and repair, vascular autoregulation, and control of vascular tone by secretion of both relaxant and contractile factors (1, 2). Endothelial cells are known to possess a broad spectrum of ion channels that open in response to a variety of stimuli, including membrane potential, receptor occupation, elevation of [Ca 2ϩ

Tetracycline rapidly penetrates the aortic wall, but the concentration achieved may be insufficient to alter collagen turnover through limitation of MMP production or activity.

Vasomotor responses and tissue ATP concentration indicate that the viability of saphenous vein can be maintained for up to 90 min in an ex vivo flow circuit and the CD31 staining indicated endothelial preservation. This opens up the possibility of investigating the early changes in saphenous vein endothelium following exposure to arterial pressure, as at bypass surgery. First results suggest that there is rapid upregulation of the leukocyte adhesion molecule ICAM-1, which can be prevented by limiting the circumferential deformation of the vein with an external PTFE stent.