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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:925.)
© 2008 American Heart Association, Inc.

Cell Biology and Signaling

Long Pentraxin 3, a Key Component of Innate Immunity, Is Modulated by High-Density Lipoproteins in Endothelial Cells

Giuseppe Danilo Norata; Patrizia Marchesi; Angela Pirillo; Patrizia Uboldi; Giulia Chiesa; Virginia Maina; Cecilia Garlanda; Alberto Mantovani; Alberico Luigi Catapano

From the Department of Pharmacological Sciences (G.D.N., P.M., A.P., P.U., G.C., A.L.C.), University of Milan, Italy; the Center for the Study of Atherosclerosis (G.D.N., A.L.C.), Società Italiana Studio Aterosclerosi, Ospedale Bassini, Cinisello Balsamo, Italy; the Istituto Clinico Humanitas (V.M., C.G., A.M.), Rozzano, Milan, Italy; and the Institute of General Pathology (A.M.), Faculty of Medicine, University of Milan, Italy.

Correspondence to Giuseppe Danilo Norata, PhD, Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy. E-mail Danilo.Norata{at}unimi.it

Abstract

Objective— High-density lipoproteins (HDL) are endowed with cardiovascular protective activities. In addition to their role in reverse cholesterol transport, HDL exert several beneficial effects on endothelial cells, including the induction of endothelial nitric oxide synthase and prostacyclin release, and the control of the immune and inflammatory response.

Methods and Results— To identify possible mechanisms involved in these effects we investigated the modulation of the expression of acute phase proteins of the pentraxin superfamily, such as C-reactive protein (CRP), serum amyloid P component protein (SAP), and the long pentraxin 3 (PTX3) by HDL in human endothelial cells. HDL induced PTX3 mRNA expression and protein release, whereas no effect was observed on CRP and SAP expression. This effect was mainly dependent on the activation of the lysosphingolipids receptors-PI3K/Akt axis and was mimicked by sphingosine 1 phosphate and other S1P mimetics. This observation was confirmed in vivo; indeed an increased expression of PTX3 mRNA was detected in the aorta of transgenic mice overexpressing human apoA-I, compared to apoA-I knock-out mice. Furthermore, plasma levels of PTX3 significantly increased in C57BL/6 mice injected with HDL.

Conclusions— These data suggest that part of the atheroprotective effects of HDL could result from the modulation of molecules that act as sensors of the immunoinflammatory balance in the vascular wall.

Here we report that HDL modulate the expression of PTX3, a member of the acute phase proteins superfamily, in vitro and in vivo. Our data suggest that part of the atheroprotective effects of HDL could result from the modulation of molecules that act as sensors of the immuno-inflammatory balance in the vascular wall.

Key Words: PTX3 • HDL • endothelium • S1P

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HDL, PTX3, and Vascular Protection

Ziad Mallat and Alain Tedgui
Arterioscler. Thromb. Vasc. Biol. 2008 28: 809-811. [Full Text] [PDF]

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				Z. Mallat and A. Tedgui HDL, PTX3, and Vascular Protection Arterioscler. Thromb. Vasc. Biol., May 1, 2008; 28(5): 809 - 811. [Full Text] [PDF]