title: Long pentraxin PTX3 upregulates tissue factor expression in human endothelial cells: a novel link between vascular inflammation and clotting activation.
abstract: 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-1beta and tumor necrosis factor-alpha, 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 IkappaBalpha. 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.
authors: Antonio Taticchi Unit for Atherosclerosis and Thrombosis, Department of Vascular Medicine and Pharmacology, Istituto Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, S. Maria Imbaro, Italy.
authors: Emanuela
authors: E
authors: Napoleone
authors: Angelomaria
authors: A
authors: Di Santo
authors: Antonio
authors: A
authors: Bastone
authors: Giuseppe
authors: G
authors: Peri
authors: Alberto
authors: A
authors: Mantovani
authors: Giovanni
authors: G
authors: de Gaetano
authors: Maria Benedetta
authors: MB
authors: Donati
authors: Roberto
authors: R
authors: Lorenzet
mesh_terms: D000209:Acute-Phase Proteins / Q000502:physiology*; D000941:Antigens / Q000502:physiology; D001777:Blood Coagulation / Q000502:physiology*; D002097:C-Reactive Protein / Q000502:physiology*; D002469:Cell Separation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D019281:Dimerization; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D020672:I-kappa B Proteins; D007249:Inflammation / Q000209:etiology / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D020569:Proto-Oncogene Proteins c-rel / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D000683:Serum Amyloid P-Component / Q000502:physiology*; D013925:Thromboplastin / Q000096:biosynthesis* / Q000502:physiology; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins; D015854:Up-Regulation / Q000502:physiology*; D000099153:Pentraxins
chemical_list: D000209:Acute-Phase Proteins; D000941:Antigens; D002097:C-Reactive Protein; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B; D020569:Proto-Oncogene Proteins c-rel; D012333:RNA, Messenger; D000683:Serum Amyloid P-Component; D013925:Thromboplastin; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D000099153:Pentraxins; C000606204:NFKBIA protein, human