Aspirin Inhibits Nuclear Factor–κB Mobilization and Monocyte Adhesion in Stimulated Human Endothelial Cells

Weber, Christian; Erl, Wolfgang; Pietsch, Angelika; Weber, Peter

doi:10.1161/01.cir.91.7.1914

Cited by 249 publications

(158 citation statements)

References 18 publications

Supporting

Mentioning

148

Contrasting

Unclassified

Order By: Relevance

“…ICAM-1 following initial upregulation by oxLDL and heparan sulfate proteoglycans (16). Consistently, ICAM-1 mAb only slightly inhibits monocyte adhesion to oxLDLtreated vascular smooth muscle cells despite induction of ICAM-1, and blocking one endothelial ligand marginally affects monocyte binding to cytokine-stimulated HUVEC, whereas combinations of mAbs cause strong inhibition (20,21), indicating that alternative ligands can compensate for blocking one interaction. An inhibition of adhesion with M1P in combination with ICAM-1 mAbs suggests a contribution of ligands for monocytes, which are also induced by mmLDL and can be blocked with M1P (14).…”

Section: Monocyte Adhesion To Oxidized Low Density Lipoprotein-stimulmentioning

confidence: 81%

Effects of Oxidized Low Density Lipoprotein, Lipid Mediators and Statins on Vascular Cell Interactions

Weber¹,

Erl²,

Weber³

et al. 1999

CCLM

Self Cite

View full text Add to dashboard Cite

The integrin heterodimer CD11b/CD18 (␣M␤2, Mac-1, CR3) expressed on monocytes or polymorphonuclear leukocytes (PMN) is a receptor for iC3b, fibrinogen, heparin, and for intercellular adhesion molecule (ICAM)-1 on endothelium, crucially contributing to vascular cell interactions in inflammation and atherosclerosis. In this report, we summarize our findings on the effects of lipid mediators and lipid-lowering drugs. Exposure of endothelial cells to oxidized low density lipoprotein (oxLDL) induces upregulation of ICAM-1 and increases adhesion of monocytic cells expressing Mac-1. Inhibition experiments show that monocytes use distinct ligands, i.e. ICAM-1 and heparan sulfate proteoglycans for adhesion to oxLDL-treated endothelium. An albumin-transferable oxLDL activity is inhibited by the antioxidant pyrrolidine dithiocarbamate (PDTC), while 8-epi-prostaglandin F2␣ (8-epi-PGF2␣) or lysophosphatidylcholine had no effect, implicating yet unidentified radicals. Sequential adhesive and signaling events lead to the firm adhesion of rolling PMN on activated and adherent platelets, which may occupy areas of endothelial denudation. Shear-resistant arrest of PMN on thrombin-stimulated platelets in flow conditions requires distinct regions of Mac-1, involving its interactions with fibrinogen bound to platelet ␣IIb␤3, and with other platelet ligands. Both arrest and adhesion strengthening under flow are stimulated by platelet-activating factor and leukotriene B4, but not by the chemokine receptor CXCR2. We tested whether Mac-1-dependent monocyte adhesiveness is affected by inhibitors of hydroxy-methylglutaryl-Coenzyme A reductase (statins) which improve morbidity and survival of patients with coronary heart disease. As compared to controls, adhesion of isolated monocytes to endothelium ex vivo was increased in patients with hypercholesterolemia. Treatment with statins decreased total and low density lipoprotein (LDL) cholesterol plasma levels, surface expression of Mac-1, and resulted in a dramatic reduction of Mac-1-mediated monocyte adhesion to endothelium. The inhibition of monocyte adhesion was reversed by mevalonate but not LDL in vitro, indicating that isoprenoid precursors are crucial for adhesiveness of Mac-1. Such effects may crucially contribute to the clinical benefit of statins, independent of cholesterol-lowering, and may represent a paradigm for novel, anti-inflammatory mechanisms of action by this class of drugs.

show abstract

Section: Monocyte Adhesion To Oxidized Low Density Lipoprotein-stimulmentioning

confidence: 81%

Effects of Oxidized Low Density Lipoprotein, Lipid Mediators and Statins on Vascular Cell Interactions

Weber¹,

Erl²,

Weber³

et al. 1999

CCLM

Self Cite

View full text Add to dashboard Cite

show abstract

“…Primers were synthesized according to sequences with minimal homology for CCR2 [24] with a product size of 557 bp, or were as described for CCR1 and CCR5 [27] or ␤-actin [28]. PCR products were analyzed by 1.25% (CCR2 and ␤-actin) or 2.0% (CCR1 and CCR5) agarose gel electrophoresis, and were quantitated by ultraviolet detection at 260 nm after separation by high-performance liquid chromatography (HPLC) on DEAE columns (Perkin-Elmer), as described in detail [28][29][30]. Respective peaks appeared at retention times predicted by molecular weight standards, and areas under the peak were integrated.…”

Section: Reverse Transcription-polymerase Chain Reaction (Rt-pcr)mentioning

confidence: 99%

Differential chemokine receptor expression and function in human monocyte subpopulations

Weber

Belge

Hundelshausen

et al. 2000

Journal of Leukocyte Biology

Self Cite

343

257

View full text Add to dashboard Cite

The subset of human blood monocytes expressing low levels of CD14 and high levels of CD16 (CD14 ؉ CD16 ؉ ) exhibits features resembling mature tissue macrophages and can be expanded in inflammatory conditions. We analyzed expression of CC chemokine receptors (CCR) in CD14 ؉ CD16 ؉ versus CD14 ؉؉ monocytes, which may be crucial for specific trafficking. Multicolor flow cytometric analysis of whole peripheral blood revealed that, as opposed to CD14 ؉؉ monocytes, the CD14 ؉ CD16 ؉ subset lacked surface expression of monocyte chemotactic protein-1 (MCP-1) receptor CCR2, however, it showed significantly higher surface expression of the macrophage inflammatory protein 1␣ (MIP-1␣)/RANTES receptor CCR5. This was paralleled by differences in mRNA expression in the subsets, as shown by reverse transcriptase-polymerase chain reaction using sorted cells. In comparison to CD14 ؉؉ monocytes, CD14 ؉ CD16 ؉ cells expressed lower CCR2 but higher CCR5 transcript levels, whereas CCR1 levels were equivalent. Flow cytometric analysis of isolated human monocytes recovered after transendothelial chemotaxis assays revealed that the percentage of CD14 ؉ CD16 ؉ cells was dramatically reduced in the fraction migrating toward MCP-1 compared with the fraction that did not migrate or the input, showing that polarized CCR2 expression was accompanied by a differential chemotactic responsiveness. Moreover, CD11b surface expression was preferentially up-regulated by MCP-1 in CD14 ؉؉ cells but by MIP-1␣ in CD14 ؉ CD16 ؉ monocytes, confirming the functional relevance of distinct CCR expression. The characteristics of CD14 ؉ CD16 ؉ cells may reflect preactivation by cytokines and determine their predilective localization during specific inflammatory conditions or susceptibility to infection. J. Leukoc. Biol. 67: 699-704; 2000.

show abstract

“…In vascular cells, NF B has been shown to regulate the expression of vascular adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) as a part of the inflammatory response. [18][19][20] It is also known that neutralizing antibody to ICAM-1 inhibits intimal hyperplasia after balloon injury of the carotid artery in rats. 21 In this study, to evaluate the therapeutic benefit of inhibition of NF B in neointimal formation after balloon injury, we utilized synthetic double-stranded DNA with high affinity for NF B as a 'decoy' cis element to bind the transcription factor and to block the activation of genes.…”

Section: And Vcam-was Markedly Decreased In Blood Vessels Transfectedmentioning

confidence: 99%

“…From this viewpoint, we focused on adhesion molecules, as it is known that NFkB regulates the expression of ICAM-1 and VCAM-1, [18][19][20] whose expression is increased in vascular cells after balloon injury. 15,25 Upregulation of these adhesion molecules is considered to be closely implicated in neointimal thickening after arterial injury.…”

Section: Effect Of Nf B Decoy Odn Transfection On Migration Of Macropmentioning

confidence: 99%

Inhibition of intimal hyperplasia after balloon injury in rat carotid artery model using cis-element ‘decoy’ of nuclear factor-kB binding site as a novel molecular strategy

et al. 2001

View full text Add to dashboard Cite

The transcription factor, NFkB, plays a pivotal role in the coordinated transactivation of cytokine and adhesion molecule genes involved in atherosclerosis and lesion formation after vascular injury. We hypothesized that synthetic doublestranded DNA with high affinity for NFkB may be introduced as a 'decoy' cis element to bind the transcription factor, and block gene activation, resulting in an effective therapeutic agent for treating intimal hyperplasia. In vivo transfection of NFkB decoy oligodeoxynucleotides (ODN) into ballooninjured rat carotid artery resulted in the inhibition of neointimal formation at 14 days after injury as compared with vessels transfected with scrambled ODN (P Ͻ 0.01). It is of importance to note that in the vessels

show abstract

Aspirin Inhibits Nuclear Factor–κB Mobilization and Monocyte Adhesion in Stimulated Human Endothelial Cells

Abstract: Our data suggest that aspirin inhibits NF-kappa B mobilization, induction of VCAM-1 and E-selectin, and subsequent monocyte adhesion in endothelial cells stimulated by TNF, thereby providing an additional mechanism for therapeutic effects of aspirin.

Cited by 249 publications

References 18 publications

Effects of Oxidized Low Density Lipoprotein, Lipid Mediators and Statins on Vascular Cell Interactions

Effects of Oxidized Low Density Lipoprotein, Lipid Mediators and Statins on Vascular Cell Interactions

Differential chemokine receptor expression and function in human monocyte subpopulations

Inhibition of intimal hyperplasia after balloon injury in rat carotid artery model using cis-element ‘decoy’ of nuclear factor-kB binding site as a novel molecular strategy

Contact Info

Product

Resources

About