Co-localization of tissue factor and tissue factor pathway inhibitor in coronary atherosclerosis

Edited by Beat Imhof Keywords:Human umbilical vein endothelial cell C-reactive protein Tissue factor Tissue factor pathway inhibitor a b s t r a c t It was found that C-reactive protein (CRP) could significantly increase the expression and activity of tissue factor (TF), but decrease that of tissue factor pathway inhibitor (TFPI) in human umbilical vein endothelial cells (HUVECs) in dose-and time-dependent manners, which could be antagonized by PDTC and U0126. CRP could also increase protein expression of phosphorylated nuclear factor-kappaB (NF-jB), IjB-a and ERK1/2 in dose-and time-dependent manner. In addition, neutralizing antibody to CD32 (FcgammaR II) could significantly attenuate the expression and activity of TF and TFPI induced by CRP. These results suggest that CRP may promote coagulation by enhancing the expression and activity of TF and reducing that of TFPI by activating NF-jB and extracellular signal-regulated kinase via FcgammaR II.

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“…Therefore, the balance between TF and TFPI also plays pivotal role in coronary events [14][15][16][23][24][25].…”

Section: Discussionmentioning

confidence: 99%

CRP regulates the expression and activity of tissue factor as well as tissue factor pathway inhibitor via NF‐κB and ERK 1/2 MAPK pathway

et al. 2009

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“…In addition, recent morphological studies have clearly shown that endothelial cells, smooth muscle cells, and macrophages express tissue factor in human atherosclerotic plaque. 3,4 Macrophages are believed to be a major source of tissue factor. Tissue factor in endothelial cells and smooth muscle cells, however, is also considered to contribute to plaque thrombogenicity.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4] This cascade is initiated by binding of tissue factor to activated factor VII, and this complex activates factor X. Activated factor X generates thrombin and in turn thrombin cleaves fibrinogen to fibrin.…”

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confidence: 99%

Statin Prevents Tissue Factor Expression in Human Endothelial Cells

et al. 2002

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Background-Tissue factor plays a pivotal role in thrombus formation in acute coronary syndromes. However, the regulatory mechanisms underlying tissue factor expression are poorly understood. Statins are effective in patients with acute coronary syndromes. Hence, the aim of this study was to clarify in human endothelial cells the signaling pathways of thrombin-induced tissue factor expression and potential inhibitory effects of statins. Methods and Results-In human aortic endothelial cells, simvastatin prevented tissue factor induction by thrombin (4 U/mL) in a concentration-dependent manner. The increase in tissue factor activity on the cell surface was also blocked by simvastatin. Simvastatin also prevented the upregulation of tissue factor expression and activity in human aortic smooth muscle cells. Mevalonate (100 mol/L) reversed the inhibitory effect of simvastatin on tissue factor expression. Thrombin induced rapid activation of Rho A and p38 MAP kinase. The Rho-kinase inhibitor Y-27632 and the p38 MAP kinase inhibitor SB203580 prevented tissue factor induction. Akt was dephosphorylated by thrombin; the phosphoinositol 3-kinase inhibitor wortmannin enhanced its dephosphorylation as well as thrombin-induced tissue factor expression. Simvastatin prevented thrombin-induced Rho A activation but not p38 MAP kinase activation. Akt dephosphorylation by thrombin was blocked by both simvastatin and Y-27632. Conclusions-Endothelial tissue factor induction by thrombin is regulated by Rho/Rho-kinase, Akt, and p38 MAP kinase.Simvastatin prevents its induction through inhibition of Rho/Rho-kinase and activation of Akt. These findings provide new insights into the action of statins in acute coronary syndromes.

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“…6 At these sites, TF can initiate thrombotic events associated with sepsis, 4,7 cancer, 8,9 or atherosclerosis. 10,11 Multiple in vitro studies have indicated that most of the cell-exposed TF is "cryptic," thus not fully active toward coagulation, 12,13 and TF "decryption" has been proposed as the initial step in the activation of coagulation. 14 Although the molecular mechanisms of TF decryption are not completely understood, many of the stimuli that decrypt TF also increase the exposure of phosphatidylserine (PS), [15][16][17][18] which is known to enhance coagulation.…”

Section: Introductionmentioning

confidence: 99%

Extracellular protein disulfide isomerase regulates coagulation on endothelial cells through modulation of phosphatidylserine exposure

Popescu

Lupu

2010

Blood

111

115

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Tissue factor (TF) is the cellular receptor for plasma protease factor VIIa (FVIIa), and the TF-FVIIa complex initiates coagulation in both hemostasis and thrombosis. Cell surface-exposed TF is mainly cryptic and requires activation to fully exhibit the procoagulant potential. Recently, the protein disulfide isomerase (PDI) has been hypothesized to regulate TF decryption through the redox switch of an exposed disulfide in TF extracellular domain. In this study, we analyzed PDI contribution to coagulation using an in vitro endothelial cell model. In this model, extracellular PDI is detected by imaging and flow cytometry. Inhibition of cell surface PDI induces a marked increase in TF procoagulant function, whereas exogenous addition of PDI inhibits TF decryption. The coagulant effects of PDI inhibition were sensitive to annexin V treatment, suggesting exposure of phosphatidylserine (PS), which was confirmed by prothrombinase assays and direct labeling.In contrast, exogenous PDI addition enhanced PS internalization. Analysis of fluorescent PS revealed that PDI affects both the apparent flippase and floppase activities on endothelial cells. In conclusion, we identified a new mechanism for PDI contribution to coagulation on endothelial cells, namely, the regulation of PS exposure, where PDI acts as a negative regulator of coagulation. (Blood. 2010; 116(6):993-1001) IntroductionTissue factor (TF) is a transmembrane glycoprotein that binds with high affinity to the plasma protease factor VII in either zymogen (FVII) or activated form (FVIIa). The formation of the TF-FVIIa complex is crucial for initiation of coagulation, leading to thrombin generation and fibrin formation. Although the primary role of TF-FVIIa is to maintain hemostasis after vascular injury, aberrant activation of coagulation underlies thrombosis, the major cause of mortality in most industrialized countries. 1 In physiologic conditions, initiation of coagulation is maintained silent by restricting the exposure of TF to the plasma factors. 2,3 In pathologic conditions, however, TF may become exposed on the endothelium 4,5 and on circulating monocytes. 6 At these sites, TF can initiate thrombotic events associated with sepsis, 4,7 cancer, 8,9 or atherosclerosis. 10,11 Multiple in vitro studies have indicated that most of the cell-exposed TF is "cryptic," thus not fully active toward coagulation, 12,13 and TF "decryption" has been proposed as the initial step in the activation of coagulation. 14 Although the molecular mechanisms of TF decryption are not completely understood, many of the stimuli that decrypt TF also increase the exposure of phosphatidylserine (PS), [15][16][17][18] which is known to enhance coagulation. PS-independent mechanisms of TF decryption have also been postulated, such as TF self-association, 19 association with lipid rafts, [20][21][22] and the redox switch of an exposed disulfide in the membrane proximal domain of TF. 23 Protein disulfide isomerase (PDI) is an oxidoreductase 24 localized mainly in the endoplasmic reticulum (ER...

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Co-localization of tissue factor and tissue factor pathway inhibitor in coronary atherosclerosis

Cited by 78 publications

References 43 publications

CRP regulates the expression and activity of tissue factor as well as tissue factor pathway inhibitor via NF‐κB and ERK 1/2 MAPK pathway

CRP regulates the expression and activity of tissue factor as well as tissue factor pathway inhibitor via NF‐κB and ERK 1/2 MAPK pathway

Statin Prevents Tissue Factor Expression in Human Endothelial Cells

Extracellular protein disulfide isomerase regulates coagulation on endothelial cells through modulation of phosphatidylserine exposure

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