We compared U-937 cell adhesion and adhesion molecule expression in human umbilical venous (HUVECs) and arterial (HUAECs) endothelial cells exposed to tumor necrosis factor (TNF), interleukin-1, and lipopolysaccharide (LPS). TNF and LPS stimulated vascular cell adhesion molecule (VCAM)-1 surface expression and adhesion of U-937 monocyte-like cells to HUVECs but not to HUAECs. Antibody studies demonstrated that in HUVECs at least 75% of the adhesion response is VCAM-1 mediated. Interleukin-1 stimulated U-937 cell adhesion to and VCAM-1 surface expression in both HUVECs and HUAECs. Pyrrolidinedithiocarbamate and the proteasome inhibitor MG-132 blocked TNF- and LPS-stimulated U-937 cell adhesion to HUVECs. These agents also significantly decreased TNF- and LPS-stimulated increases in HUVEC surface VCAM-1. TNF increased VCAM-1 protein and mRNA in HUVECs that was blocked by pyrrolidinedithiocarbamate. However, neither TNF or LPS stimulated VCAM-1 expression in HUAECs. TNF stimulated expression of both intercellular adhesion molecule-1 and E-selectin in HUVECs, but in HUAECs, only intercellular adhesion molecule-1 was increased. Electrophoretic mobility shift assays demonstrated no difference in the pattern of TNF-stimulated nuclear factor-κB activation between HUVECs and HUAECs. These studies demonstrate a novel and striking insensitivity of arterial endothelium to the effects of TNF and LPS and indicate a dissociation between the ability of HUAECs to upregulate nuclear factor-κB and VCAM-1.

The objective of this study was to assess the effects of two structurally distinct yet selective proteasome inhibitors (PS-341 and lactacystin) on leukocyte adhesion, endothelial cell adhesion molecule (ECAM) expression, and nuclear factor-κB (NF-κB) activation in tumor necrosis factor (TNF)-α-stimulated human umbilical vein endothelial cells (HUVEC) and the transformed, HUVEC-derived, ECV cell line. We found that TNF (10 ng/ml) significantly enhanced U-937 and polymorphonuclear neutrophil (PMN) adhesion to HUVEC but not to ECV; TNF also significantly enhanced surface expression of vascular cell adhesion molecule 1 and E-selectin (in HUVEC only), as well as intercellular adhesion molecule 1 (ICAM-1; in HUVEC and ECV). Pretreatment of HUVEC with lactacystin completely blocked TNF-stimulated PMN adhesion, partially blocked U-937 adhesion, and completely blocked TNF-stimulated ECAM expression. Lactacystin attenuated TNF-stimulated ICAM-1 expression in ECV. Pretreatment of HUVEC with PS-341 partially blocked TNF-stimulated leukocyte adhesion and ECAM expression. These effects of lactacystin and PS-341 were associated with inhibitory effects on TNF-stimulated NF-κB activation in both HUVEC and ECV. Our results demonstrate the importance of the 26S proteasome in TNF-induced activation of NF-κB, ECAM expression, and leukocyte-endothelial adhesive interactions in vitro.

We conclude that densitometric evaluation allows differentiation of the various possible components of carotid plaque. The determination of plaque composition, based on density measurement, may provide information about its potential for thromboembolization.

Only a small subset of patients with combined superficial femoral artery and vein injuries results in amputation. The importance of the venous component as a risk factor for amputation is uncertain. Ligation vs. reconstruction of venous injuries is controversial. For clarification of these issues, we analyzed retrospectively multiple risk factors for amputation in combined superficial femoral artery and vein injuries in a civilian population. There were 25 patients treated in a 20-year period. Sixteen injuries were caused by small caliber missiles, six by shotgun blasts, and three by knife wounds. Three patients (12%) ultimately underwent amputation. The major risk factor for amputation was method of vascular reconstruction. All three amputations underwent ligation of the superficial femoral vein with arterial reconstruction by placement of a reversed interposition saphenous vein graft (p = 0.0009). None of the remaining 22 patients with salvaged limbs underwent reconstruction by this combination of techniques. Consequently, the authors emphasize the importance of venous reconstruction, particularly in combined injuries with major arterial involvement requiring interposed grafts.