Oxidized low-density lipoprotein impairs the anti-coagulant function of tissue-factor-pathway inhibitor through oxidative modification by its high association and accelerated degradation in cultured human endothelial cells

Horie, Shuichi; Hiraishi, Sayuri; Hirata, Yukiyo; Kazama, Mutsuyoshi; Matsuda, Juzo

doi:10.1042/bj3520277

Cited by 15 publications

(9 citation statements)

References 52 publications

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“…The administration of recombinant TFPI or of the TFPI gene into animal models has demonstrated that TFPI is a useful anticoagulant for preventing the thrombogenicity of vascular wall cells. The relationship of TFPI with oxidized LDL 76,77 and with Lp(a) 78 has been demonstrated.…”

Section: Potential Roles Of Tfpi In Atherogenesismentioning

confidence: 99%

Regulation of Functions of Vascular Wall Cells by Tissue Factor Pathway Inhibitor

Kato

2002

ATVB

143

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Abstract-Tissue factor pathway inhibitor (TFPI) is a Kunitz-type protease inhibitor that inhibits the initial reactions of blood coagulation. A major pool of TFPI is the form associated with the surface of endothelial cells, which is speculated to play an important role in regulating the functions of vascular wall cells. TFPI consists of 3 tandem Kunitz inhibitor domains, the first and second of which inhibit the tissue factor-factor VIIa complex and factor Xa, respectively. Recent findings indicate that TFPI has another function, ie, the modulation of cell proliferation. This function is based on the interaction of the C-terminal region of TFPI with these cells. Key Words: tissue factor pathway inhibitor Ⅲ blood coagulation Ⅲ thrombosis Ⅲ restenosis Ⅲ vascular wall cells B lood coagulation is initiated by the interaction of factor VII in plasma with tissue factor (TF) at the site of blood vessel injury, and the TF-factor VIIa complex activates factor X and factor IX, leading to the generation of thrombin. Vascular wall cells play a central role in the regulation of hemostasis by the cellular control of procoagulant and anticoagulant mechanisms. Normal endothelial cells do not show detectable levels of TF, although expression of endothelial TF occurs in vitro after perturbation with different agonists. On the other hand, increased TF levels have been detected in atherosclerotic plaque, probably reflecting secretion by smooth muscle cells, monocytes/macrophages, and endothelial cells.The TF pathway inhibitor (TFPI) is a Kunitz-type protease inhibitor that inhibits the initial reactions of blood coagulation. A major pool of TFPI is the form associated with the surface of endothelial cells, which is speculated to play an important role in the regulation of the functions of vascular wall cells. Recent findings indicate that TFPI has another function, ie, the modulation of cell proliferation. Many reviews on TFPI have been published. [1][2][3][4][5] The structure and biology of TFPI have recently been reviewed. 6 Recent findings related to regulation of the functions of vascular wall cells by TFPI in physiological and pathological conditions will be summarized in the present review. Functional Domains of TFPIEver since the determination of the amino acid sequence of human TFPI 14 years ago, 7 a number of studies have been published on the structure and functions of TFPI. The amino acid sequences of TFPI from monkeys, rabbits, dogs, rats, and mice have been reported. Many investigators have examined the properties of TFPI by using recombinant proteins. As shown in Figure 1, TFPI mRNA is expressed from the TFPI gene, which consists of 9 exons. Mature TFPI protein consists of 3 tandem Kunitz inhibitor domains, the first and second of which inhibit TF-VIIa and Xa, respectively. The third domain has no inhibitory activity toward proteases. Heparin-binding sites of TFPI are located in the third Kunitz domain and the C-terminal basic region. The inhibitory effect of TFPI on the initiation of blood coagulation and the enhanc...

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Section: Potential Roles Of Tfpi In Atherogenesismentioning

confidence: 99%

Regulation of Functions of Vascular Wall Cells by Tissue Factor Pathway Inhibitor

Kato

2002

ATVB

143

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“…fatty acid and cholesterol [1] , leads to the formation of foam cells (macrophages laden with cholesterol) and interferes with the activity of an endothelial coagulation inhibitor [through modification and degradation of tissue factor (TF) pathway inhibitor], thereby promoting local coagulation [2] .…”

mentioning

confidence: 99%

The Role of Complement in the Development and Manifestation of Murine Atherogenic Inflammation: Novel Avenues

Francescut

Steiner²,

Byrne³

et al. 2011

J Innate Immun

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Atherosclerosis is a chronic progressive inflammatory disease which manifests in the arterial vascular tree. It is a major cause of cardiovascular morbidity and contributes significantly to mortality in the developed world. Triggers for this inflammatory process are elevated levels of cholesterol, bacterial infection and obesity. The immune response in atherosclerosis is essentially pro-atherogenic, leading to lipid accumulation and cellular changes within the arterial wall. Small-animal models of atherosclerosis are used to study the relevance of candidate factors (cells, genes, diets) in the development and progression of lesions. From a multidisciplinary viewpoint, there are challenges and limitations to this approach. Activation of complement determines or modifies the outcome of acute and chronic inflammation. This review dissects the role of complement in the early development as well as the progressive manifestation of murine atherosclerosis and the advances in knowledge provided by the use of specific mouse models. It gives a critical overview of existing models, analyses seemingly conflicting results obtained with complement-deficient mouse models, highlights the importance of interrelationships between pro-coagulpant activity, adipose tissue, macrophages and complement, and uncovers exciting avenues of topical research.

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“…Recently Ettelaie et al (19) reported that the TFPI-dependent inhibition of TF activity was reduced when a mixture of LDL and rTFPI or TFPI derived from Hep G2 cells, not derived from plasma, was oxidized, and they suggested that the oxidation of LDL might mask lysine and arginine residues within the Kunitz domains of TFPI. We have shown that free TFPI derived from human umbilical vein endothelial cells or rTFPI associates with ox-LDL, but not with native or acetylated LDL, and we proposed that association between TFPI and ox-LDL might cause structural alteration of the TFPI molecule, leading to impairment of inhibitory activity on FX activation (20). In order to understand the physiological function of TFPI under pathological conditions, such as increase in oxidation of LDL in plasma and in the vascular bed, it is important to establish the precise mechanism of the association of TFPI with ox-LDL.…”

Section: Introductionmentioning

confidence: 94%

“…LDL and oxidized LDL were prepared as described previously (20). Briefly, LDL was incubated with 10 M CuSO 4 for 12 h at 37°C and 200 M EDTA was added.…”

Section: Modification Of Ldlmentioning

confidence: 99%

Oxidized Low-density Lipoprotein Associates Strongly with Carboxy-terminal Domain of Tissue Factor Pathway Inhibitor and Reduces the Catalytic Activity of the Protein

Horie¹,

Hiraishi²,

Hamuro³

et al. 2002

Thromb Haemost

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SummaryTissue factor pathway inhibitor (TFPI) is a physiological protease inhibitor of the extrinsic blood coagulation pathway. Previously we have shown that TFPI associates quite rapidly with oxidized lowdensity lipoprotein (ox-LDL), with a reduction of the inhibitory activity on factor X activation. In the present study, it was found, by means of agarose gel electrophoresis, that the pre-incubation of full-length rTFPI with heparin or the carboxy (C)-terminal part (peptide 240-265) of TFPI prevented the association with ox-LDL in a dose-dependent manner. When rTFPI lacking the C-terminal basic part of the molecule (rTFPI-C) was mixed with ox-LDL, only a small amount of rTFPI-C was shifted to the position of ox-LDL on electrophoresis. Further, ox-LDL did not reduce the activity of rTFPI-C. These results indicate that the C-terminal domain of TFPI molecule plays a predominant role in the binding to ox-LDL and the binding through the C-terminal part is essential for the ox-LDL-dependent reduction of the anticoagulant activity of TFPI.

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Oxidized low-density lipoprotein impairs the anti-coagulant function of tissue-factor-pathway inhibitor through oxidative modification by its high association and accelerated degradation in cultured human endothelial cells

Cited by 15 publications

References 52 publications

Regulation of Functions of Vascular Wall Cells by Tissue Factor Pathway Inhibitor

Regulation of Functions of Vascular Wall Cells by Tissue Factor Pathway Inhibitor

The Role of Complement in the Development and Manifestation of Murine Atherogenic Inflammation: Novel Avenues

Oxidized Low-density Lipoprotein Associates Strongly with Carboxy-terminal Domain of Tissue Factor Pathway Inhibitor and Reduces the Catalytic Activity of the Protein

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