Effects of cross-linking ICAM-1 on the surface of human vascular smooth muscle cells: induction of VCAM-1 but no proliferation.

OBJECTIVE: Intercellular adhesion molecule (ICAM)-1 is an immunoglobulin-like cell adhesion molecule expressed by several cell types, including proliferating vascular smooth muscle cells (VSMC). Cross-linking ICAM-1 on the surface of different cell types has previously been shown to cause an increase in cellular activation within the cytoplasm. Here, our objective was to examine events following ligation of ICAM-1 on the surface of human VSMC. METHODS: VSMC were isolated by explant from human pulmonary arteries or aortic tissue from cardiac transplant donors. ICAM-1 was ligated with monoclonal antibodies, followed by cross-linking with a secondary antibody. Activation of signalling pathways, proliferation and expression of a second adhesion molecule, vascular cell adhesion molecule (VCAM)-1 were investigated. RESULTS: ICAM-1 cross-linking caused an increase in activation of extracellular regulated kinase (Erk)-1/-2 and Jun N-terminal kinase (JNK)-1/-2. mRNA and protein for VCAM-1 was observed after ICAM-1 cross-linking, and this was abrogated by addition of an upstream inhibitor of Erk-1/-2, PD98059. No increase in cell proliferation was observed. CONCLUSIONS: Ligation of ICAM-1 on the surface of vascular smooth muscle cells in vitro, leads to the expression of adhesion molecules associated with monocyte infiltration, but does not contribute to smooth muscle cell proliferation. In vivo, this might lead to prolongation of the inflammatory response within diseased blood vessels, by arresting monocytes within atherosclerotic plaques.

Antivimentin antibodies are an independent predictor of transplant-associated coronary artery disease after cardiac transplantation.

BACKGROUND: Transplant-associated coronary artery disease (TxCAD) is the most serious long-term complication after cardiac transplantation. Anti-endothelial antibodies are associated with disease, and one of the major endothelial antigens recognized in the sera of patients has been shown to be the protein filament vimentin. In this study, we investigated whether antivimentin antibodies are associated with TxCAD and whether their presence can be used to identify patients at high risk of developing angiographically detectable TxCAD. METHODS: Up to 5 years after transplantation, 880 sequential sera (7.07+/-1.8 samples/patient) were collected retrospectively from 109 patients; the majority were collected in the first 2 years. Sera were assessed for antivimentin antibodies using ELISA. TxCAD was assessed by annual angiography. RESULTS: Mean titres of antivimentin antibodies, calculated up to 1, 2, and 5 years, were significantly higher in patients who developed TxCAD than those who remained disease free (P<0.0001, P<0.0038, and P<0.0001, respectively). A predictive test based on the first-year mean vimentin titre alone (> or = 120) produced a test with 63% sensitivity and 76% specificity. Inclusion of persistent rejection or high 1-year mean titre (> or = 270) as a risk factor produced a test with 66% sensitivity and 82% specificity. Multivariate analysis of time to occurrence of transplant vasculopathy showed that mean titre at 1 or 2 years was an independent predictor of time until disease in the presence of all other variables. CONCLUSIONS: Antivimentin antibodies are an independent predictor of TxCAD and can be used to identify some of the patients who are at high risk of developing this complication.

Failure of orally administered hydroxychloroquine sulphate to prevent venous thromboembolism following elective hip operations.

In a double-blind, randomized trial of orally administered hydroxychloroquine sulphate in the prevention of venous thromboembolism after elective surgery on the hip, the drug or a placebo was given to fifty consecutive patients. Therapy was commenced on the day before the operation and continued for fourteen days. The diagnosis of deep venous thrombosis was made by daily thermographic scanning of the legs and confirmed by phlebography. The diagnosis of pulmonary embolism was made by perfusion lung scanning. No significant difference in the incidence of thromboembolism was found between treated and control groups. The results provide evidence that substances which reduce the incidence of thromboembolism in general surgery may not be effective in operations on the hip.

Serum fibrin(ogen) degradation products in diagnosis of deep-vein thrombosis and pulmonary embolism after hip surgery.

Levels of fibrin(ogen) degradation products (F.D.P.) have been measured by radioimmunoassay for degradation product E (FgE) and by tanned-red-cell haemagglutination-inhibition immunoassay (T.R.C.H.I.I.) in the serum of thirty-three patients undergoing total hip replacement. Levels of F.D.P. did not correlate with thermographic evidence of deep-venous thrombosis. However, in 34 patients with pulmonary embolism, levels of F.D.P. measured by the T.R.C.H.I.I. were transiently raised at the time of embolus, and FgE concentrations were increased for up to 5 days preceding the embolus. Since the measurments of FgE is simple, convenient, and cheap, this estimation might constitute a valuable screening test for major thromboembolic episodes in the postoperative period.