Disease relevance of F3

• Tissue factor (TF) initiates coagulation and its expression in vascular smooth muscle cells (VSMC) likely plays a role in the propagation of arterial thrombosis [1].
• Activation of the coagulation system and increased expression of tissue factor (TF) in pulmonary fibrosis associated with acute and chronic lung injury have been previously documented [2].
• CONCLUSIONS: These results suggest that TF plays an important role in the development of renal injury after ischemia and reperfusion [3].
• Tissue factor (TF) plays a critical role in the pathogenesis of disseminated intravascular coagulation (DIC) observed in patients with septic shock [4].
• CONCLUSIONS: The results indicate that AS-1/TF inhibited the ischemia-reperfusion injury of the kidney [5].

High impact information on F3

• VSMC may play a role in the generation or propagation of thrombus through the induction of TF, particularly in settings, such as those associated with acute vessel injury, where the endothelium is denuded and the VSMC are exposed to circulating blood [6].
• To investigate whether medial vascular smooth muscle provides a source of TF following arterial injury, the induction of TF mRNA and protein was studied in balloon-injured rat aorta [7].
• These data demonstrate that vascular injury rapidly induces active TF in arterial smooth muscle, providing a procoagulant that may result in thrombus initiation or propagation [7].
• TF is not expressed in the intima or media of normal adult blood vessels [6].
• In contrast to other growth factor-responsive genes, such as KC and c-fos, downregulation of protein kinase C activity by prolonged treatment with phorbol esters fails to block agonist-mediated TF induction [6].

Chemical compound and disease context of F3

• This is the first report showing that direct inhibition of TF-mediated coagulation activation abrogates bleomycin-induced pulmonary fibrosis [2].
• The imbalance between TF and TFPI seems to be important in promoting fibrin thrombus formation in the lung of endotoxin induced DIC condition [8].
• Tissue factor (TF) is a low molecular weight glycoprotein that initiates the clotting cascade and is considered to be a major regulator of coagulation, hemostasis, and thrombosis [6].
• We hypothesized that blockade of TF-factor VIIa (FVIIa) complex would decrease lung inflammation and proinflammatory cytokine release after tracheal instillation of Escherichia coli lipopolysaccharide (LPS 0111:B4) [9].
• The loss of luminal TF into the circulation may attenuate thrombosis at sites of arterial injury [10].

Biological context of F3

• A difference in the quantitative expression of TF and TFPI is a new distinctive feature of SMC phenotypes [11].
• We report cloning the cDNA and proximal promoter region of the rat TF gene [1].
• Moreover, vasodilatation, as well as enhanced fibrinolytic activity, may help to prevent rats from severe organ dysfunction in the TF-induced DIC model [12].
• While maintaining the general structure and organization of the TF molecule, there is a surprising divergence (approximately 18%) between the derived amino acid sequences of the rat and mouse TF [1].
• The microparticles (MPs) produced during SMC death bore intact and functional TF, but the release of TFPI did not change, so that the balance shifted to a procoagulant state during apoptosis [13].

Anatomical context of F3

• Tissue factor (TF) and its specific inhibitor TF pathway inhibitor (TFPI) are produced by vascular smooth muscle cells (SMCs) in vitro and are increased in vivo in atherosclerotic compared to normal vessels [11].
• Furthermore, we observed that fluorescein-labeled AS-1/TF was absorbed into endothelial cells [14].
• The studies confirm the important role of TF-mediated coagulation in the smooth muscle proliferation and neointimal thickening that follows vascular injury and suggest that the anticoagulant effect alone of TFPI and TFPI-related proteins is sufficient to explain their therapeutic action [15].
• BACKGROUND: Tissue factor (TF) is an initiation factor for blood coagulation, and its expression is induced on macrophages and endothelial cells during the inflammatory or immune responses [16].
• In an immunohistochemical study, an increase in number of monocytes in the microvasculature was observed after LPS injection, and many of these cells (> 90%) were positive for TF antigen [17].

Associations of F3 with chemical compounds

• Experimental DIC was induced by sustained infusion of 0.1, 1, 10, or 50 mg/kg lipopolysaccharide (LPS), or 3.75 U/kg thromboplastin (TF), for 4 h via the rat tail vein [12].
• The inductions of TF and PAI-1 mRNAs were inhibited by a 5-HT1/5-HT2 receptor antagonist (methiothepin) and a selective 5-HT2A receptor antagonist (MCI-9042) [18].
• These inductions were accompanied by increases in PAI-1 and TF activities and were inhibited by a type I Ang II receptor antagonist [19].
• BACKGROUND: Tissue factor (TF) is a membrane-bound glycoprotein that is the primary cellular initiator of the blood clotting cascade and its expression is induced on macrophages and endothelial cells during the inflammatory or immune response [3].
• Furthermore, since those mRNA inductions by BK were enhanced by nitro-L-arginine-methyl ester (L-NAME) and attenuated by L-arginine (L-Arg), NO was speculated to negatively contribute to the expressions of TF and PAI-1 [20].

Regulatory relationships of F3

• TFPI is a multivalent Kunitz-type protease inhibitor that inhibits factor Xa via its second Kunitz domain and the factor VIIa/tissue factor (TF) complex via its first Kunitz domain [15].

Other interactions of F3

• The activities of TF and PAI-1 were also measured [18].
• Age-related decline of F3/contactin in rat hippocampus [21].

Analytical, diagnostic and therapeutic context of F3

• Using this protocol in combination with real-time PCR, we found that stroke significantly increased mRNA levels of protease-activated receptor 1 (PAR-1) and tissue factor (TF) in ECs isolated from ischemic cerebral microvessels compared with nonischemic vessels [22].
• We designed an antisense oligodeoxynucleotide (AS-1/TF) for rat TF and studied its effect on hepatic ischemic reperfusion injury [14].
• Although TF was strongly stained on endothelial cells and Kupffer cells accumulating to the site of the necrosis in the control group, the area of the necrosis and the grade of TF staining were significantly reduced in the TFPI-treated group [16].
• We have investigated age-related change in the expression of F3 mRNA and protein in the Wistar rat brain using immunohistochemistry and in situ hybridization [21].
• In situ hybridization with a 35S-labeled antisense rat TF cRNA probe detected TF mRNA in the adventitia but not in the media or endothelium of uninjured aorta [7].

References