Upregulation of pentraxin-3 in human endothelial cells after lysophosphatidic acid exposure.
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.
Gustin
Cindy
C
Laboratory of Biochemistry and Cellular Biology, University of Namur, 61, rue de Bruxelles, 5000 Namur, Belgium. cindy.gustin@fundp.ac.be
Delaive
Edouard
E
Dieu
Marc
M
Calay
Damien
D
Raes
Martine
M
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
D002097:C-Reactive Protein; D008246:Lysophospholipids; D012333:RNA, Messenger; D049368:Receptors, Lysophosphatidic Acid; D000683:Serum Amyloid P-Component; D000099153:Pentraxins; C032881:lysophosphatidic acid