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(Circulation. 2009;120:699-708.)
© 2009 American Heart Association, Inc.

Vascular Medicine

Deficiency of the Long Pentraxin PTX3 Promotes Vascular Inflammation and Atherosclerosis

Giuseppe Danilo Norata, PhD; Patrizia Marchesi, MSc; Vivek Krishna Pulakazhi Venu, MSc; Fabio Pasqualini, BS; Achille Anselmo, PhD; Federica Moalli, MSc; Irene Pizzitola, MSc; Cecilia Garlanda, VetScD; Alberto Mantovani, MD, PhD; Alberico Luigi Catapano, PhD

From the Departments of Pharmacological Sciences (G.D.N., P.M., V.K.P.V., I.P., A.L.C.) and Translational Medicine (A.M.), Università degli Studi di Milano, Milan; Center for the Study of Atherosclerosis, Società Italiana Studio Aterosclerosi, Ospedale Bassini, Cinisello Balsamo (G.D.V., A.L.C.); and Istituto Clinico Humanitas, IRCCS, Rozzano, Milan (F.P., A.A., F.M., C.G., A.M.), Italy.

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

Received July 15, 2008; accepted June 5, 2009.

Background— Immune responses participate in several phases of atherosclerosis; there is, in fact, increasing evidence that both adaptive immunity and innate immunity tightly regulate atherogenesis. Pentraxins are a superfamily of acute-phase proteins that includes short pentraxins such as C-reactive protein or long pentraxins such as PTX3, a molecule acting as the humoral arm of innate immunity. To address the potential role of PTX3 in atherogenesis, we first investigated the expression of PTX3 during atherogenesis, generated double-knockout mice lacking PTX3 and apolipoprotein E, and then studied the effect of murine PTX3 deficiency on plasma lipids, atherosclerosis development, and gene expression pattern in the vascular wall.

Methods and Results— PTX3 expression increases in the vascular wall of apolipoprotein E–knockout mice from 3 up to 18 months of age. Double-knockout mice lacking PTX3 and apolipoprotein E were fed an atherogenic diet for 16 weeks. Aortic lesions were significantly increased in double-knockout mice and mice heterozygous for PTX3 compared with apolipoprotein E–knockout mice. Mice lacking PTX3 showed a more pronounced inflammatory profile in the vascular wall as detected by cDNA microarray and quantitative polymerase chain reaction analysis and an increased macrophage accumulation within the plaque. Finally, lesion size correlated with the number of bone marrow monocytes.

Conclusion— PTX3 has atheroprotective effects in mice, which, in light of the cardioprotective effects recently reported, suggests a cardiovascular protective function of the long pentraxin 3 through the modulation of the immunoinflammatory balance in the cardiovascular system.

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Clinical Summaries
Circulation 2009 120: 647-648. [Extract] [Full Text]