scholarly journals Oxidized low-density lipoprotein-induced microparticles promote endothelial monocyte adhesion via intercellular adhesion molecule 1

2017 ◽  
Vol 313 (5) ◽  
pp. C567-C574 ◽  
Author(s):  
Zhiwei Fu ◽  
Enchen Zhou ◽  
Xu Wang ◽  
Mingda Tian ◽  
Jian Kong ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecule ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Adhesion Assay ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Intercellular Adhesion Molecule 1

Oxidized low-density lipoprotein (oxLDL) accumulates early in atherosclerotic lesions and plays an important role in the progressive formation of atherosclerotic plaques. Endothelial derived microparticles (EMPs) form a heterogeneous population of <1-μm particles that shed from endothelial membranes upon activation. While EMPs are shown to be involved in atherosclerotic pathophysiology and progression, there is no report regarding the relationship between oxLDL and EMPs. In this study, we aim to determine the influence of oxLDL on endothelial microparticle release and the subsequent regulation of the endothelial activation. EMPs were collected from the medium of human umbilical vein endothelial cells (HUVECs) treated with oxLDL or PBS as control. We find that oxLDL increases the release of EMPs containing intercellular adhesion molecule 1 (ICAM-1) but not vascular cell adhesion molecule 1 (VCAM-1). Confocal microscopy analysis further demonstrates that these EMPs interact with endothelial cells and increase the expression of ICAM-1 in HUVECs. The fact that injecting oxLDL-induced EMPs via the tail vein of ICR mice augments ICAM-1 expression on aortic endothelial cells confirms our results in vivo. Finally, oxLDL-induced EMPs from HUVECs increase the adhesion of monocytes to endothelial cells as determined by the adhesion assay. Our study suggests that oxLDL may augment the release of EMPs harboring increased levels of ICAM-1 that can be transferred to endothelial cells elsewhere. This leads to increased monocyte recruitment in other regions where oxLDL accumulation was initially more limited. EMPs may therefore serve as the mediator that propagates oxLDL-induced endothelial inflammation.

scholarly journals Exogenous NO enhances hydrogen peroxide-mediated neutrophil adherence to cultured endothelial cells

1998 ◽  
Vol 274 (5) ◽  
pp. L820-L826 ◽  
Author(s):  
Naotsuka Okayama ◽  
Hiroshi Ichikawa ◽  
Laura Coe ◽  
Makoto Itoh ◽  
J. Steven Alexander
Keyword(s):  
Hydrogen Peroxide ◽  
Endothelial Cells ◽  
Adhesion Molecule ◽  
Platelet Activating Factor ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Adhesion Assay ◽  
Intercellular Adhesion Molecule 1 ◽  
No Donor ◽  
Cultured Endothelial Cells

One important aspect of oxidant injury is the enhancement of neutrophil-endothelial adhesion by oxidants such as hydrogen peroxide. Recent studies suggest that nitric oxide (NO) can limit oxidant-mediated tissue injury, since inhibitors of endogenous NO synthesis often promote neutrophil-endothelial adhesion. However, less is known about the direct role of exogenous NO in modulating proadhesive effects of oxidants. The objective of this study was to examine how an NO donor modifies hydrogen peroxide-mediated adhesion of neutrophils to cultured endothelial cells. Human umbilical vein endothelial cell monolayers were exposed for 30 min to 0–0.1 mM hydrogen peroxide with or without the NO donor spermine-NONOate (SNO; 0–0.5 mM), and the adhesion of51Cr-labeled polymorphonuclear neutrophils (PMNs) was measured in a static adhesion assay. PMN adherence was not altered by either peroxide (up to 0.1 mM) or SNO (up to 0.5 mM) alone but was significantly increased by over 300% by coadministration of both 0.1 mM peroxide and 0.5 mM SNO. This increase in adhesion with these two agents was correlated with an increase in the presentation of surface P-selectin but not intercellular adhesion molecule-1. Both PMN adhesion and P-selectin presentation were blocked by 0.1 mM desferrioxamine (an iron chelator) and 1 mM methionine (an oxy-radical scavenger). WEB-2086, a platelet-activating factor-receptor antagonist (10 μM), also prevented PMN adhesion but not P-selectin expression. An antibody directed against either P-selectin or intercellular adhesion molecule-1 also blocked adhesion. These data indicate that NO may actually exacerbate rather than protect against the inflammatory effects of peroxide in some models of inflammation through the synthesis of platelet-activating factor and the mobilization of P-selectin.

Endothelin-1 plus oxidized low-density lipoprotein, but neither alone, increase human monocyte adhesion to endothelial cells

2001 ◽  
Vol 101 (6) ◽  
pp. 731-738 ◽  
Author(s):  
M.R. LANGENFELD ◽  
S. NAKHLA ◽  
A.K. DEATH ◽  
W. JESSUP ◽  
D.S. CELERMAJER
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Adhesion Molecule ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Human Monocytes ◽  
Oxidized Low Density Lipoprotein ◽  
Endothelin 1

Endothelin-1 is a potent vasoconstrictor and mitogenic peptide that is implicated in the atherosclerosis of apolipoprotein E-deficient mice and may promote atherogenesis in humans. We hypothesized that endothelin-1 might promote the adhesion of monocytes to endothelial cells, a key early event in atherosclerosis. We investigated the adhesion of primary human monocytes (isolated by elutriation) to human umbilical vein endothelial cell cultures after incubation with endothelin-1 (0.1 and 0.01nM; approximately physiological concentrations), copper-oxidized low-density lipoprotein (LDL) (0.1mg/ml) and a combination of the two. After a 4h incubation with 0.1 or 0.01nM endothelin-1 combined with oxidized LDL, adhesion was increased to 120±4% (P < 0.001 compared with control) and 118±4% (P < 0.002) respectively, whereas neither substance alone increased adhesion (92-104% of control values; not significant). Neither endothelin receptor A blockade nor co-incubation with anti-fibronectin antibody inhibited the pro-adhesive effects of endothelin-1 plus oxidized LDL (115±7% and 115±3% of control compared with 120±4% respectively; not significant). Endothelial cell expression of intercellular adhesion molecule-1, vascular adhesion molecule-1 and E-selectin were unchanged throughout the experiment. Therefore physiological concentrations of endothelin-1 and oxidized LDL may act synergistically to increase the adhesion of human monocytes to endothelial cells, contributing in part to the observed pro-atherogenic effects of endothelin-1.

Homocysteine and Oxidized Low Density Lipoprotein Enhance Platelet Adhesion to Endothelial Cells under Flow Conditions: Distinct Mechanisms of Thrombogenic Modulation

2000 ◽  
Vol 83 (02) ◽  
pp. 338-344 ◽  
Author(s):  
D. Varon ◽  
I. Tamarin ◽  
A. Zivelin ◽  
O. Salomon ◽  
B. Shenkman ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Platelet Adhesion ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Intercellular Adhesion Molecule ◽  
Αvβ3 Integrin ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Flow Conditions ◽  
Enhancing Effect

SummaryWe investigated the effects of two well established risk factors for cardiovascular disease, homocysteine and oxidized low density lipoprotein (ox-LDL), on endothelial cell thrombogenicity. For this purpose we studied platelet adhesion to human endothelial cells (EC) under flow conditions at a shear rate of 350 s−1 following EC treatment with either homocysteine or ox-LDL. Treatment of EC with either homocysteine (1 or 10 mmol/L for 16 h) or ox-LDL (100 µg/ml for 16 h) resulted in a 2-3 fold enhancement in platelet adhesion. The enhancement in platelet adhesion induced by 1 mmol/L homocysteine, but not that induced by 10 mmol/L homocysteine, was absolutely dependent on fibrin formation. Homocysteine treatment has significantly increased the cell surface tissue factor (TF) activity and slightly reduced the expression of the intercellular adhesion molecule I (ICAM-1). In contrast, ox-LDL treatment upregulated ICAM-1 expression and had no significant effect on endothelial TF activity. Neither homocysteine nor Ox-LDL affected surface expression of the αvβ3 integrin. The homocysteine-induced enhancement in platelet adhesion was almost completely abolished by blockade of the EC TF activity by a polyclonal antibody. The enhancing effect of homocysteine was also greatly reduced by inhibition of the EC αvβ3 integrin, but was not affected by blockade of EC ICAM-1. On the other hand, ox-LDL-induced enhancement in platelet – EC adhesion was greatly inhibited by blocking ICAM-1 or αvβ3, but remained unaffected by inhibition of TF activity. Preincubation of platelets with the glycoprotein IIb-IIIa (GPIIb-IIIa) antagonist Reo-Pro has virtually abolished the enhancing effect of both homocysteine and ox-LDL. Our results suggest that homocysteine and ox-LDL might increase endothelial thrombogenicity by distinct mechanisms: homocysteine – by inducing TF activity, and ox-LDL – by upregulating ICAM-1, both of which enhance GPIIb-IIIa/fibrinogen dependent platelet adhesion to EC. The αvβ3 integrin, although not affected by EC stimulation, seems to play a crucial role in platelet-EC interaction regardless of the mechanism of EC perturbation.

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