Alterations in the structure of apolipoprotein B-100 determine the behaviour of LDL towards thromboplastin

Ettelaie, Camille; Haris, Parvez I.; James, N. J.; Wilbourn, Barry; Adam, J. M.; Bruckdorfer, K. Richard

doi:10.1016/s0005-2760(96)00185-3

Cited by 12 publications

(19 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…37 This domain is within a region of ApoB100 capable of local structural alterations that changes even at low levels of LDL oxidation. 20 Moreover, the oxidation of lipids alone (Table 2), or the addition of pure lipid peroxides, did not enhance the tissue factor activity, but rather inhibited it slightly, concurring with our previous report that the enhancement of tissue factor activity by oxidized LDL arises from the modification of ApoB100. 7 The inactivation of TFPI as a result of oxidation of lipoprotein has been demonstrated previously.…”

Section: Ettelaie Et Al Inhibition Of Tissue Factor By Apob100 and Tfpisupporting

confidence: 90%

“…It has been shown that such variation can also be attributed to differences in the composition of the lipoproteins. 7,20 However, the overall pattern of inhibition, exhibiting 2 distinct peaks (Figure 1) was the same in all the sera examined. By using antibodies specific to ApoB100 and TFPI, it was shown that the first inhibitory peak was the result of TFPI activity, whereas ApoB100 had a slower, more prolonged effect on tissue factor procoagulant activity.…”

Section: Ettelaie Et Al Inhibition Of Tissue Factor By Apob100 and Tfpimentioning

confidence: 79%

“…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%

“…7 The formation of lysine adducts 19 and alterations in the secondary and tertiary structure of this protein affects the residues within the domain responsible for inhibition of tissue factor. 20 It has also been shown that the inhibitory potential of TFPI may be compromised by lipoprotein oxidation. 21 The first 2 Kunitz domains within TFPI responsible for inhibiting clotting factors VIIa and Xa contain lysine and arginine residues at the inhibition sites.…”

mentioning

confidence: 99%

See 3 more Smart Citations

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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Ettelaie Et Al Inhibition Of Tissue Factor By Apob100 and Tfpisupporting

confidence: 90%

Section: Ettelaie Et Al Inhibition Of Tissue Factor By Apob100 and Tfpimentioning

confidence: 79%

“…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%

mentioning

confidence: 99%

See 2 more Smart Citations

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

Self Cite

View full text Add to dashboard Cite

show abstract

“…For example, oxidized PCs are avidly hydrolyzed by PLA 2 , followed by removal of most lipolytic products by albumin. This leads to complex structural changes that can increase solvent exposure of the apolar groups on LDL surface and promote aggregation, fusion, and ultimate disintegration of LDLs (59, 72, 73). …”

Section: Biochemical Modificationsmentioning

confidence: 99%

Aggregation and fusion of low-density lipoproteins in vivo and in vitro

Gursky

2013

BioMolecular Concepts

View full text Add to dashboard Cite

Low-density lipoproteins (LDLs, also known as ‘bad cholesterol’) are the major carriers of circulating cholesterol and the main causative risk factor of atherosclerosis. Plasma LDLs are 20- to 25-nm nanoparticles containing a core of cholesterol esters surrounded by a phospholipid monolayer and a single copy of apolipoprotein B (550 kDa). An early sign of atherosclerosis is the accumulation of LDL-derived lipid droplets in the arterial wall. According to the widely accepted ‘response-to-retention hypothesis’, LDL binding to the extracellular matrix proteoglycans in the arterial intima induces hydrolytic and oxidative modifications that promote LDL aggregation and fusion. This enhances LDL uptake by the arterial macrophages and triggers a cascade of pathogenic responses that culminate in the development of atherosclerotic lesions. Hence, LDL aggregation, fusion, and lipid droplet formation are important early steps in atherogenesis. In vitro, a variety of enzymatic and nonenzymatic modifications of LDL can induce these reactions and thereby provide useful models for their detailed analysis. Here, we summarize current knowledge of the in vivo and in vitro modifications of LDLs leading to their aggregation, fusion, and lipid droplet formation; outline the techniques used to study these reactions; and propose a molecular mechanism that underlies these pro-atherogenic processes. Such knowledge is essential in identifying endogenous and exogenous factors that can promote or prevent LDL aggregation and fusion in vivo and to help establish new potential therapeutic targets to decelerate or even block these pathogenic reactions.

show abstract

Tissue factor upregulation drives a thrombosis–inflammation circuit in relation to cardiovascular complications

Chu

2006

Cell Biochem. Funct.

View full text Add to dashboard Cite

The extrinsic coagulation is recognized as an 'inducible' signalling cascade resulting from tissue factor (TF) upregulation by exposure to clotting zymogen FVII upon inflammation or tissue injury. Following the substantial initiation, an array of proteolytic activation generates mediating signals (active serine proteases: FVIIa, FXa and FIIa) that lead to hypercoagulation with fibrin overproduction manifesting thrombosis. In addition, TF upregulation plays a central role in driving a thrombosis-inflammation circuit. Coagulant mediators (FVIIa, FXa and FIIa) and endproduct (fibrin) are proinflammatory, eliciting tissue necrosis factor, interleukins, adhesion molecules and many other intracellular signals in different cell types. Such resulting inflammation could ensure 'fibrin' thrombosis via feedback upregulation of TF. Alternatively, the resulting inflammation triggers platelet/leukocyte/polymononuclear cell activation thus contributing to 'cellular' thrombosis. TF is very vulnerable to upregulation resulting in hypercoagulability and subsequent thrombosis and inflammation, either of which presents cardiovascular risks. The prevention and intervention of TF hypercoagulability are of importance in cardioprotection. Blockade of inflammation reception and its intracellular signalling prevents TF expression from upregulation. Natural (activated protein C, tissue factor pathway inhibitor, or antithrombin III) or pharmacological anticoagulants readily offset the extrinsic hypercoagulation mainly through FVIIa, FXa or FIIa inhibition. Therefore, anticoagulants turn off the thrombosis-inflammation circuit, offering not only antithrombotic but anti-inflammatory significance in the prevention of cardiovascular complications.

show abstract

Alterations in the structure of apolipoprotein B-100 determine the behaviour of LDL towards thromboplastin

Cited by 12 publications

References 46 publications

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

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

Aggregation and fusion of low-density lipoproteins in vivo and in vitro

Tissue factor upregulation drives a thrombosis–inflammation circuit in relation to cardiovascular complications

Contact Info

Product

Resources

About