on December 27, 2007
Published online before print December 27, 2007, doi: 10.1161/ATVBAHA.107.158642
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Submitted on September 3, 2007
Accepted on December 13, 2007
Upregulation of Pentraxin-3 in Human Endothelial Cells After Lysophosphatidic Acid Exposure
Cindy Gustin *;
From the Laboratory of Biochemistry and Cellular Biology, University of Namur (FUNDP), Belgium.
* To whom correspondence should be addressed. E-mail: cindy.gustin{at}fundp.ac.be.
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 NF
B 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.
Key words: lysophosphatidic acid • endothelial cell • atherosclerosis • Pentraxin-3 • chemoattractant
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