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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:491.)
© 2008 American Heart Association, Inc.

Cell Biology/Signaling

Upregulation of Pentraxin-3 in Human Endothelial Cells After Lysophosphatidic Acid Exposure

Cindy Gustin; Edouard Delaive; Marc Dieu; Damien Calay; Martine Raes

From the Laboratory of Biochemistry and Cellular Biology, University of Namur (FUNDP), Belgium.

Correspondence to Cindy Gustin, Department of Biochemistry and Cellular Biology, University of Namur (FUNDP), 61, rue de Bruxelles, 5000 Namur, Belgium. E-mail cindy.gustin{at}fundp.ac.be

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 NFB 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.

Starting from a 2D-gel analytical approach, we demonstrated a LPA-induced pentraxin-3 overexpression in endothelial cells. LPA- but also oxLDL-induced pentraxin-3 upregulation was reduced in the presence of an antagonist of the LPA-receptors and was largely dependent on NFB activation. Finally, we demonstrated the chemotactic activity of pentraxin-3 on monocytes THP-1.

Key Words: lysophosphatidic acid • endothelial cell • atherosclerosis • Pentraxin-3 • chemoattractant

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