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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:782.)
© 2002 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Long Pentraxin PTX3 Upregulates Tissue Factor Expression in Human Endothelial Cells

A Novel Link Between Vascular Inflammation and Clotting Activation

Emanuela Napoleone; Angelomaria Di Santo; Antonio Bastone; Giuseppe Peri; Alberto Mantovani; Giovanni de Gaetano; Maria Benedetta Donati; Roberto Lorenzet

From the "Antonio Taticchi" Unit for Atherosclerosis and Thrombosis, Department of Vascular Medicine and Pharmacology, Istituto Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud (E.N., A.D.S., G.d.G., M.B.D., R.L.), S. Maria Imbaro; the Department of Immunology and Cell Biology, Istituto di Ricerche Farmacologiche Mario Negri (A.B., G.P., A.M.), Milano; and Istituto di Patologia Generale (A.M), University of Milano, Milano, Italy. Dr de Gaetano is now at Centro di Ricerche e Alta Formazione, Università Cattolica, Campobasso, Italy.

Correspondence to Dr Roberto Lorenzet, Consorzio Mario Negri Sud, Via Nazionale, 66030 S. Maria Imbaro, Italy. E-mail lorenzet{at}cmns.mnegri.it

Inflammation is a major contributing factor to atherosclerotic plaque development and ischemic heart disease. PTX3 is a long pentraxin that was recently found to be increased in patients with acute myocardial infarction. Because tissue factor (TF), the in vivo trigger of blood coagulation, plays a dominant role in thrombus formation after plaque rupture, we tested the possibility that PTX3 could modulate TF expression. Human umbilical vein endothelial cells, incubated with endotoxin (lipopolysaccharide) or the inflammatory cytokines interleukin-1ß and tumor necrosis factor-, expressed TF. The presence of PTX3 increased TF activity and antigen severalfold in a dose-dependent fashion. PTX3 exerted its effect at the transcription level, inasmuch as the increased levels of TF mRNA, mediated by the stimuli, were enhanced in its presence. The increase in mRNA determined by PTX3 originated from an enhanced nuclear binding activity of the transacting factor c-Rel/p65, which was mediated by the agonists and measured by electrophoretic mobility shift assay. The mechanism underlying the increased c-Rel/p65 activity resided in an enhanced degradation of the c-Rel/p65 inhibitory protein IB. In the area of vascular injury, during the inflammatory response, cell-mediated fibrin deposition takes place. Our results suggest that PTX3, by increasing TF expression, potentially plays a role in thrombogenesis and ischemic vascular disease.

Key Words: tissue factor • PTX3 • inflammation • coagulation • endothelial cells

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