Upregulation of pentraxin-3 in human endothelial cells after lysophosphatidic acid exposure

Research output: Contribution to journalArticle

Abstract

Objective: The earliest event in atherogenesis appears to be endothelium dysfunction. Lysophosphatidic acid (LPA), one of the major bioactive lipid components of oxidized low-density lipoproteins (oxLDL), can cause the activation of endothelial cells (ECs), which start to secrete multiple proinflammatory polypeptides/proteins. The purpose of this study was to better document the proatherogenic properties of LPA using a subproteomic approach focused on the secretome of LPA-treated ECs. Methods and Results: The secretome of LPA-treated ECs was analyzed using the 2D-DIGE approach. Among the 20 spots displaying significant variations of abundance compared with the control cells, we identified pentraxin-3 by mass spectrometry. Pentraxin-3 upregulation was confirmed at the mRNA and protein level, both on immortalized and primary ECs. LPA- but also oxLDL-induced pentraxin-3 upregulation was reduced in the presence of an antagonist of the LPA-receptors and largely dependent on NFkB activation. Finally, we demonstrated, for the first time, the chemotactic activity of pentraxin-3 on human THP-1 monocytes by using a chemotaxis assay. Conclusions: Our findings favor the proatherogenic role of LPA, a bioactive lipid produced by activated platelets and present in oxLDL, because it enhances pentraxin-3 secretion that could contribute to the accumulation of monocytes in the atherosclerotic lesion. © 2008 American Heart Association, Inc.

Original languageEnglish
Pages (from-to)491-497
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume28
Issue number3
DOIs
Publication statusPublished - 1 Mar 2008

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Up-Regulation
Endothelial Cells
Monocytes
Lysophosphatidic Acid Receptors
Two-Dimensional Difference Gel Electrophoresis
Lipids
Chemotaxis
Endothelium
lysophosphatidic acid
PTX3 protein
Mass Spectrometry
Atherosclerosis
Proteins
Blood Platelets
Messenger RNA
Peptides
oxidized low density lipoprotein

Keywords

  • Atherosclerosis
  • Chemoattractant
  • Endothelial cell
  • Lysophosphatidic acid
  • Phentraxin-3

Cite this

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title = "Upregulation of pentraxin-3 in human endothelial cells after lysophosphatidic acid exposure",
abstract = "Objective: The earliest event in atherogenesis appears to be endothelium dysfunction. Lysophosphatidic acid (LPA), one of the major bioactive lipid components of oxidized low-density lipoproteins (oxLDL), can cause the activation of endothelial cells (ECs), which start to secrete multiple proinflammatory polypeptides/proteins. The purpose of this study was to better document the proatherogenic properties of LPA using a subproteomic approach focused on the secretome of LPA-treated ECs. Methods and Results: The secretome of LPA-treated ECs was analyzed using the 2D-DIGE approach. Among the 20 spots displaying significant variations of abundance compared with the control cells, we identified pentraxin-3 by mass spectrometry. Pentraxin-3 upregulation was confirmed at the mRNA and protein level, both on immortalized and primary ECs. LPA- but also oxLDL-induced pentraxin-3 upregulation was reduced in the presence of an antagonist of the LPA-receptors and largely dependent on NFkB activation. Finally, we demonstrated, for the first time, the chemotactic activity of pentraxin-3 on human THP-1 monocytes by using a chemotaxis assay. Conclusions: Our findings favor the proatherogenic role of LPA, a bioactive lipid produced by activated platelets and present in oxLDL, because it enhances pentraxin-3 secretion that could contribute to the accumulation of monocytes in the atherosclerotic lesion. {\circledC} 2008 American Heart Association, Inc.",
keywords = "Atherosclerosis, Chemoattractant, Endothelial cell, Lysophosphatidic acid, Phentraxin-3",
author = "Cindy Gustin and Edouard Delaive and Marc Dieu and Damien Calay and Martine Raes",
note = "Publication code : RES. ACAD.",
year = "2008",
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day = "1",
doi = "10.1161/ATVBAHA.107.158642",
language = "English",
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journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",
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publisher = "Lippincott Williams and Wilkins",
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TY - JOUR

T1 - Upregulation of pentraxin-3 in human endothelial cells after lysophosphatidic acid exposure

AU - Gustin, Cindy

AU - Delaive, Edouard

AU - Dieu, Marc

AU - Calay, Damien

AU - Raes, Martine

N1 - Publication code : RES. ACAD.

PY - 2008/3/1

Y1 - 2008/3/1

N2 - Objective: The earliest event in atherogenesis appears to be endothelium dysfunction. Lysophosphatidic acid (LPA), one of the major bioactive lipid components of oxidized low-density lipoproteins (oxLDL), can cause the activation of endothelial cells (ECs), which start to secrete multiple proinflammatory polypeptides/proteins. The purpose of this study was to better document the proatherogenic properties of LPA using a subproteomic approach focused on the secretome of LPA-treated ECs. Methods and Results: The secretome of LPA-treated ECs was analyzed using the 2D-DIGE approach. Among the 20 spots displaying significant variations of abundance compared with the control cells, we identified pentraxin-3 by mass spectrometry. Pentraxin-3 upregulation was confirmed at the mRNA and protein level, both on immortalized and primary ECs. LPA- but also oxLDL-induced pentraxin-3 upregulation was reduced in the presence of an antagonist of the LPA-receptors and largely dependent on NFkB activation. Finally, we demonstrated, for the first time, the chemotactic activity of pentraxin-3 on human THP-1 monocytes by using a chemotaxis assay. Conclusions: Our findings favor the proatherogenic role of LPA, a bioactive lipid produced by activated platelets and present in oxLDL, because it enhances pentraxin-3 secretion that could contribute to the accumulation of monocytes in the atherosclerotic lesion. © 2008 American Heart Association, Inc.

AB - Objective: The earliest event in atherogenesis appears to be endothelium dysfunction. Lysophosphatidic acid (LPA), one of the major bioactive lipid components of oxidized low-density lipoproteins (oxLDL), can cause the activation of endothelial cells (ECs), which start to secrete multiple proinflammatory polypeptides/proteins. The purpose of this study was to better document the proatherogenic properties of LPA using a subproteomic approach focused on the secretome of LPA-treated ECs. Methods and Results: The secretome of LPA-treated ECs was analyzed using the 2D-DIGE approach. Among the 20 spots displaying significant variations of abundance compared with the control cells, we identified pentraxin-3 by mass spectrometry. Pentraxin-3 upregulation was confirmed at the mRNA and protein level, both on immortalized and primary ECs. LPA- but also oxLDL-induced pentraxin-3 upregulation was reduced in the presence of an antagonist of the LPA-receptors and largely dependent on NFkB activation. Finally, we demonstrated, for the first time, the chemotactic activity of pentraxin-3 on human THP-1 monocytes by using a chemotaxis assay. Conclusions: Our findings favor the proatherogenic role of LPA, a bioactive lipid produced by activated platelets and present in oxLDL, because it enhances pentraxin-3 secretion that could contribute to the accumulation of monocytes in the atherosclerotic lesion. © 2008 American Heart Association, Inc.

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KW - Chemoattractant

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KW - Lysophosphatidic acid

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