Cyclosporin A inhibits monocyte tissue factor activation in cardiac transplant recipients

Circulation
H HölschermannW Haberbosch

Abstract

Fibrin deposition and thrombosis have been implicated in both allograft rejection and vasculopathy after cardiac transplantation. Because monocytes play a pivotal role in the pathophysiology of intravascular coagulation activation through their ability to synthesize tissue factor (TF), we asked (1) whether monocyte TF activation occurs in cardiac transplant recipients and (2) whether monocyte TF expression is affected by treatment with cyclosporin A (CsA). We measured levels of TF activity in peripheral blood mononuclear cells and highly purified monocytes/macrophages from 10 consecutive cardiac transplant recipients and 10 healthy control subjects. TF activity generated by both unstimulated and endotoxin-stimulated cells was significantly higher in transplant recipients than in control subjects (P<.05). Increased monocyte TF expression in transplant recipients was shown to be adversely affected by treatment with CsA: TF induction was markedly reduced by CsA serum concentrations reaching peak CsA drug levels. Inhibition of TF induction in the presence of high CsA blood concentrations was also observed when stimulation of cells was performed with interferon-gamma or interleukin-1beta. As shown by reverse transcription-polymerase...Continue Reading

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Citations

Jul 17, 1999·Atherosclerosis·E TremoliS Colli
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Jan 23, 1999·The American Journal of Pathology·H HölschermannW Haberbosch

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