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.
  
  
  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 NFkappaB 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.
authors.affiliation: Laboratory of Biochemistry and Cellular Biology, University of Namur, 61, rue de Bruxelles, 5000 Namur, Belgium. cindy.gustin@fundp.ac.be
authors.forename: Cindy
authors.initials: C
authors.lastname: Gustin
authors.forename: Edouard
authors.initials: E
authors.lastname: Delaive
authors.forename: Marc
authors.initials: M
authors.lastname: Dieu
authors.forename: Damien
authors.initials: D
authors.lastname: Calay
authors.forename: Martine
authors.initials: M
authors.lastname: Raes
mesh_terms: D000704:Analysis of Variance; D050197:Atherosclerosis / Q000503:physiopathology; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D005786:Gene Expression Regulation; D006801:Humans; D015151:Immunoblotting; D008246:Lysophospholipids / Q000494:pharmacology*; D011336:Probability; D012333:RNA, Messenger / Q000032:analysis; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics / Q000378:metabolism*; D012680:Sensitivity and Specificity; D000683:Serum Amyloid P-Component / Q000235:genetics / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology; D015854:Up-Regulation; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D008246:Lysophospholipids; D012333:RNA, Messenger; D049368:Receptors, Lysophosphatidic Acid; D000683:Serum Amyloid P-Component; D000099153:Pentraxins; C032881:lysophosphatidic acid