The inhibition of thromboplastin by apolipoprotein-B and the effect of various associated lipids

Ettelaie, Camille; Howell, Roy M.

doi:10.1016/0049-3848(92)90033-7

Cited by 7 publications

(8 citation statements)

References 30 publications

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“…Therefore, we propose that the interaction of apo B-100 with tissue factor is essentially similar in nature to that with its receptor. KRAD-14 peptide was an efficient inhibitor of tissue factor, and the rate of inhibition was much faster than that observed with either LDL or apo B-100 [5][6][7][8]10]. This may be due to the immense size of apo B-100 and LDL.…”

Section: Discussionmentioning

confidence: 86%

“…Following clot formation, the procoagulant effect of tissue factor is restrained by a number of circulating inhibitors within the serum, including tissue-factor-pathway inhibitor (TFPI) [3] and apolipoprotein (apo) A-II within high-density lipoprotein (HDL) [4]. The ability of low-density lipoprotein (LDL) to inhibit the procoagulant activity of tissue factor arises from direct interaction of the protein moieties of tissue factor and LDL (apo B-100) [5][6][7][8]. The inhibition of tissue factor by LDL occurs at a slower rate, but persists longer than that of TFPI [6,8].…”

Section: Introductionmentioning

confidence: 99%

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Identification of a domain in apolipoprotein B-100 that inhibits the procoagulant activity of tissue factor

Ettelaie

James

Adam

et al. 1998

Biochemical Journal

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The ability of low-density lipoprotein (LDL) to inhibit the procoagulant activity of tissue factor is mediated by a direct protein-protein interaction involving apolipoprotein (apo) B-100. A lysine-rich sequence within apo B-100 (residues 3121-3217), which we have termed lysine-rich apo B-100-derived (KRAD)-98 peptide, may be responsible for its activity. Within this region, residues 3147-3160 (KRAD-14) contain an exceptionally high proportion of positive amino acids. Both recombinant KRAD-98 and KRAD-14 peptides inhibited the procoagulant activity of tissue factor by preventing the activation of factor VII. KRAD-14 also inhibited the prothrombinase components, factors Xa and V. In comparison with the parent protein (apo B-100), KRAD-14 peptide displayed a 20-fold enhancement in the rate of inhibition, whereas KRAD-98 peptide exhibited a rate closer to that of apo B-100. Mutational analysis of KRAD-14 peptide revealed three adjacent amino acids, alteration of which greatly reduced the inhibitory potential of this peptide. A peptide derived from tissue factor (residues 58-66) was found to act co-operatively with tissue factor itself, but also augmented the inhibition of tissue-factor activity by apo B-100. In conclusion, LDL may be a physiological regulator of haemostatic mechanisms through the interactions of lysine-rich domains of apo B-100 with tissue factor.

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Section: Discussionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Identification of a domain in apolipoprotein B-100 that inhibits the procoagulant activity of tissue factor

Ettelaie

James

Adam

et al. 1998

Biochemical Journal

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“…6 Conversely, incubation of preparations of LDL with anti-human TFPI antibodies does not completely suppress the inhibitory potential of the complex. 33 The inhibition pattern of tissue factor by serum Minimally modified LDL 68Ϯ10 30Ϯ8 Ϫ10Ϯ5…”

Section: Discussionmentioning

confidence: 99%

“…The protein was then reconstituted in lipids resembling those found in native LDL (nLDL) as described previously. 6,7 In earlier studies, it was shown that the LDL-resembling particle (LDL-r) has a similar composition, electrophoretic mobility, and protein fold to nLDL. 20 …”

Section: Preparation Of Ldl and Apob100 And Preparation Of And Reconsmentioning

confidence: 99%

“…ApoB100 was isolated as before 6,7 and examined on a 5% (wt/vol) denaturing polyacrylamide 23 to ensure the homogeneity. Moreover, the nature of the protein was examined by immunoprecipitation, using antibodies against human ApoB100 (Immuno Ltd) and antibodies against human TFPI (American Diagnostics) to ensure its purity.…”

Section: Preparation Of Ldl and Apob100 And Preparation Of And Reconsmentioning

confidence: 99%

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Comparison of the Inhibitory Effects of ApoB100 and Tissue Factor Pathway Inhibitor on Tissue Factor and the Influence of Lipoprotein Oxidation

Ettelaie

Wilbourn

Adam

et al. 1999

ATVB

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Abstract-The procoagulant activity of tissue factor is regulated by circulating inhibitors such as tissue factor pathway inhibitor (TFPI) and LDL. These 2 inhibitors also readily associate making the distinction between their activities difficult. We have examined the relative contributions of intact and C-terminal truncated TFPI and ApoB100. By following the inhibitory potential of the preparations, over a period of 120 minutes, it was demonstrated that TFPI and LDL-resembling particles inhibited tissue factor at different rates. TFPI was found to be a short, fast-acting inhibitor, whereas the action of LDL-resembling particles was more prolonged but slower. The oxidation of LDL has been closely associated with the development of cardiovascular disease, including atherosclerosis and thrombosis. Positively charged amino acids, particularly lysine residues, are prone to alterations via the formation of adducts by lipid peroxidation products. These residues are important in the inhibition of tissue factor activity by ApoB100. They also play an important role in the inhibitory Kunitz domains of TFPI. We have shown that the decline in the ability of LDL to inhibit tissue factor was as a result of modifications in LDL arising from oxidation. By examining the effects of oxidation on full-length and C-terminal truncated TFPI bound to LDL-resembling particles, we found that TFPI is only affected when in close association with ApoB100. C-terminal truncated TFPI was not affected significantly by oxidation. Finally, chemical modification of lysine and arginine residues reduced the overall inhibition of tissue factor by TFPI. We propose that TFPI and LDL act separately to inhibit tissue factor in vivo. However, the oxidation of LDL can alter both the endogenous activity of ApoB100 and reduce that of closely associated TFPI, compromising normal hemostasis.

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Lipid levels and risk of venous thrombosis: results from the MEGA-study

et al. 2017

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The relationship between lipid levels and risk of venous thrombosis is not well established. We aimed to assess the association between several lipids and risk of venous thrombosis using data from a population-based case–control study, and to evaluate the underlying mechanism, considering confounding by common risk factors and mediation via hemostatic factors and C-reactive protein. From the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA) study, 2234 patients with a first venous thrombosis and 2873 controls were included. Percentile categories of total/low-density lipoprotein/high-density lipoprotein cholesterol, triglycerides, and apolipoproteins B and A1 were established in controls (<10th, 10th–25th, 25th–75th [reference], 75th–90th, >90th percentile). In age- and sex-adjusted models, decreasing levels of apolipoproteins B and A1 were dose-dependently associated with increased thrombosis risk, with odds ratios of 1.35 (95% confidence interval 1.12–1.62) and 1.50 (95% confidence interval 1.25–1.79) for the lowest category versus the reference category, respectively. The dose–response relation remained with further adjustment for body mass index, estrogen use, statin use, and diabetes. Although apolipoproteins B and A1 were associated with several hemostatic factors and C-reactive protein, none explained the increased risk in mediation analyses. The other lipids were not associated with venous thrombosis risk. In conclusion, decreasing levels of apolipoproteins B and A1 were associated with increased risk of venous thrombosis. Our findings are consistent with experimental data on the anticoagulant properties of apolipoproteins B and A1. These findings need to be confirmed and the underlying mechanism further investigated.Electronic supplementary materialThe online version of this article (doi:10.1007/s10654-017-0251-1) contains supplementary material, which is available to authorized users.

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The inhibition of thromboplastin by apolipoprotein-B and the effect of various associated lipids

Cited by 7 publications

References 30 publications

Identification of a domain in apolipoprotein B-100 that inhibits the procoagulant activity of tissue factor

Identification of a domain in apolipoprotein B-100 that inhibits the procoagulant activity of tissue factor

Comparison of the Inhibitory Effects of ApoB100 and Tissue Factor Pathway Inhibitor on Tissue Factor and the Influence of Lipoprotein Oxidation

Lipid levels and risk of venous thrombosis: results from the MEGA-study

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