Oxidized Phospholipids in Oxidized Low-Density Lipoprotein Reduce the Activity of Tissue Factor Pathway Inhibitor Through Association with Its Carboxy-Terminal Region

Ohkura, Naoki; Hiraishi, Sayuri; Itabe, Hiroyuki; Hamuro, Tsutomu; Kamikubo, Yu-ichi; Takano, Tatsuya; Matsuda, Juzo; Horie, Shuichi

doi:10.1089/1523086041361686

Cited by 43 publications

(35 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…MM-LDL was shown to regulate all of these activities to promote a procoagulant state. 2,28,[39][40][41][42] The signal transduction pathway regulating the induction of TF mRNA levels by Ox-PAPC in HUVEC was shown to be mediated through both a PKC/Erk/EGR-1 pathway and a Ca++/calcineurin/NFAT pathway. 39 Both transcription factors, EGR-1 and NFAT, act together in regulating the TF promoter.…”

Section: Procoagulant Activitymentioning

confidence: 99%

“…These studies demonstrate differential regulation of TF and TM transcription by Ox-PAPC, mediated through activation of distinct and separate signaling pathways. In addition, Ox-PAPC was also show to reduce the activity of tissue factor pathway inhibitor (TFPI), a protease inhibitor that inhibits the initial reactions of blood coagulation 42 . In these studies, it was concluded that TFPI activity was inhibited through direct interaction of oxidized lipids with the C-terminal basic region of TFPI.…”

Section: Procoagulant Activitymentioning

confidence: 99%

See 1 more Smart Citation

Endothelial cell regulation by phospholipid oxidation products

Berliner

Gharavi

2008

Free Radical Biology and Medicine

View full text Add to dashboard Cite

Oxidized phospholipids accumulate in atherosclerotic lesions, on lipoproteins, in other states of chronic inflammation, on apoptotic cells, necrotic cells and cells exposed to oxidative stress. These lipids regulate the transcription of over 1000 gene, regulating many endothelial functions, by activating several different cell surface receptors and multiple signaling pathways. These lipids also have important effects not involving transcription that regulate cell junctions and leukocyte binding. Thus these lipids are potent regulators of endothelial cell function with broad effects comparable in extent but differing from those of cytokines.

show abstract

Section: Procoagulant Activitymentioning

confidence: 99%

Section: Procoagulant Activitymentioning

confidence: 99%

Endothelial cell regulation by phospholipid oxidation products

Berliner

Gharavi

2008

Free Radical Biology and Medicine

View full text Add to dashboard Cite

show abstract

“…Oxidized phospholipids were also shown to accumulate in atherosclerosis and other chronic inflammatory diseases (5). The increased concentrations of oxidized phospholipids in the injured lung may influence the functions of pulmonary endothelial cells (ECs), including the modulation of pulmonary inflammatory response and EC barrier regulation (6-9).Oxidized phospholipids may induce various proinflammatory effects, including the stimulation of cytokines and chemokine production (10, 11), the activation of cell adhesion molecules (12, 13), the elevation of intracellular and extracellular levels of superoxide radicals in human ECs (14, 15), the activation of coagulation cascades, and platelet activation (16,17). However, in addition to tissue-damaging and proinflammatory effects, oxidized phospholipid products may exhibit potent anti-inflammatory activities under certain conditions.…”

mentioning

confidence: 99%

Differential Regulation of Endothelial Cell Permeability by High and Low Doses of Oxidized 1-Palmitoyl-2-Arachidonyl-sn-Glycero-3-Phosphocholine

Starosta

Zimman

et al. 2012

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

The generation of phospholipid oxidation products in atherosclerosis, sepsis, and lung pathologies affects endothelial barrier function, which exerts significant consequences on disease outcomes in general. Our group previously showed that oxidized 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphocholine (OxPAPC) at low concentrations increases endothelial cell (EC) barrier function, but decreases it at higher concentrations. In this study, we determined the mechanisms responsible for the pulmonary endothelial cell barrier dysfunction induced by high OxPAPC concentrations. OxPAPC at a range of 5-20 mg/ml enhanced EC barriers, as indicated by increased transendothelial electrical resistance. In contrast, higher OxPAPC concentrations (50-100 mg/ml) rapidly increased EC permeability, which was accompanied by increased total cell protein tyrosine (Tyr) phosphorylation, phosphorylation at Tyr-418, the activation of Src kinase, and the phosphorylation of adherens junction (AJ) protein vascular endothelial cadherin (VE-cadherin) at Tyr-731 and Tyr-658, which was not observed in ECs stimulated with low OxPAPC doses. The early tyrosine phosphorylation of VE-cadherin was linked to the dissociation of VE-cadherin-p120-catenin/b-catenin complexes and VE-cadherin internalization, whereas low OxPAPC doses promoted the formation of VE-cadherin-p120-catenin/b-catenin complexes. High but not low doses of OxPAPC increased the production of reactive oxygen species (ROS) and protein oxidation. The inhibition of Src by PP2 and ROS production by N-acetyl cysteine inhibited the disassembly of VE-cadherin-p120-catenin complexes, and attenuated high OxPAPC-induced EC barrier disruption. These results show the differential effects of OxPAPC doses on VE-cadherin-p120-catenin complex assembly and EC barrier function. These data suggest that the rapid tyrosine phosphorylation of VE-cadherin and other potential targets mediated by Src and ROS-dependent mechanisms plays a key role in the dissociation of AJ complexes and EC barrier dysfunction induced by high OxPAPC doses.Keywords: endothelium; oxidized phospholipids; protein tyrosine phosphorylation; VE-cadherin; permeability Oxidative stress and the activation of phospholipases lead to the formation and accumulation of biologically active lipid oxidation products. Phospholipid oxidation products were shown to accumulate in a number of inflammatory diseases (1). An increase in oxidative stress and in phospholipid oxidation products was demonstrated in patients with diverse lung diseases, such as acute respiratory distress syndrome, ventilator-induced lung injury, and asthma, and in animal studies of lung injury (2-4). Oxidized phospholipids were also shown to accumulate in atherosclerosis and other chronic inflammatory diseases (5). The increased concentrations of oxidized phospholipids in the injured lung may influence the functions of pulmonary endothelial cells (ECs), including the modulation of pulmonary inflammatory response and EC barrier regulation (6-9).Oxidized phospholipids may induce ...

show abstract

“…In the atheromatosus lesions the TF is located around the necrotic center rich in lipids, for it is assumed that low density lipoprotein cholesterol (c-LDL) and the oxidized lipids induce the expression of TF (47).…”

Section: Alterations In Hemostasis and Fibrinolysismentioning

confidence: 99%

“…In the atheromatous lesions TF is located around the necrotic center rich in lipids, for it is assumed that c-LDL and the oxidized lipids induce the expression of TF (47). In contrast, PCR associated with inflammatory processes also induces the expression of TF on the cellular surfaces (78).…”

Section: Alterations In Hemostasis and Fibrinolysismentioning

confidence: 99%

Hemostasis alterations in metabolic syndrome (Review)

Palomo¹,

Alarcón²,

Moore‐Carrasco³

et al. 2006

Int J Mol Med

View full text Add to dashboard Cite

Abstract. Metabolic syndrome (MS) is characterized by the presence of at least three of the following alterations: enlargement of the waist diameter, higher levels of arterial pressure, low density lipoprotein cholesterol and glycemia, and reduction of high density lipoprotein cholesterol. The prevalence of MS reaches 23% in young adults, a percentage that increases with age. People with MS have a greater risk of suffering from cardiovascular disease (CVD). The physiopathologic alterations now found to exist in MS are diverse; among them is endothelial dysfunction, which triggers atherogenic lesions and hypercoagulability characterized by alterations of the coagulation factors and the regulatory proteins of fibrinolysis such as the plasminogen activator inhibitor (PAI-1). The increase in oxidative stress and/or the reactive oxygen species in patients with MS is partially related to the oxidation state of the lipoproteins, especially of the low density lipoproteins. This fact favors atherogenesis. Moreover, the oxidative stress produces alterations in the production of adipokines, cytokines secreted by the adipose tissues. The abnormality in the transport of lipoprotein diminishes the catabolism of the very low density lipoprotein (VLDL) and increases the catabolism of the high density lipoprotein (HDL), which creates insulin resistance. This process is associated with a lower concentration of adiponectin that in turn regulates the catabolism of VLDL and HDL; consequently increasing the flow of fatty acids from the adipose tissue to the liver and muscles. The proinflammatory cytokines, among them tumor necrosis factor · (TNF-·), are of great importance in MS regulating different processes and molecules such as PAI-1. PAI-1 is controlled by the group of transcription factors peroxisome proliferator-activated receptor (PPAR), especially by PPAR Á and · ligands. In summary, MS includes multiple alterations related to insulin resistance at several levels: hepatic, muscular, adipose and vascular tissue (endothelium). The exact mechanism that underlies the relationship between MS and CVD are not sufficiently known yet; pathogenic explanations are lacking for the mechanisms relating metabolic factors to insulin resistance and the association with the development of atherosclerosis and thrombosis. MS alterations and the main aspects related to homeostasis alterations are examined in this report.

show abstract

Oxidized Phospholipids in Oxidized Low-Density Lipoprotein Reduce the Activity of Tissue Factor Pathway Inhibitor Through Association with Its Carboxy-Terminal Region

Cited by 43 publications

References 34 publications

Endothelial cell regulation by phospholipid oxidation products

Endothelial cell regulation by phospholipid oxidation products

Differential Regulation of Endothelial Cell Permeability by High and Low Doses of Oxidized 1-Palmitoyl-2-Arachidonyl-sn-Glycero-3-Phosphocholine

Hemostasis alterations in metabolic syndrome (Review)

Contact Info

Product

Resources

About