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(Circulation. 2008;117:1055-1064.)
© 2008 American Heart Association, Inc.

Molecular Cardiology

Cardioprotective Function of the Long Pentraxin PTX3 in Acute Myocardial Infarction

Monica Salio, PharmD; Stefano Chimenti, PharmD; Noeleen De Angelis, BiolD; Fabiola Molla, BiolD; Virginia Maina, BiolD; Manuela Nebuloni, MD; Fabio Pasqualini, BS; Roberto Latini, MD; Cecilia Garlanda, VetScD; Alberto Mantovani, MD

From the Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy (M.S., S.C., N.D.A., F.M., R.L.); Istituto Clinico Humanitas, IRCCS, Rozzano, Italy (V.M., F.P., C.G., A.M.); Pathology Unit, "L. Sacco" Department of Clinical Sciences (M.N.) and Institute of General Pathology (A.M.), University of Milan, Milan, Italy; and Department of Medicine, New York Medical College, Valhalla (R.L.).

Correspondence to Alberto Mantovani, Istituto Clinico Humanitas, Via Manzoni 56, 20089 Rozzano, Italy. E-mail alberto.mantovani{at}humanitas.it

Received October 30, 2008; accepted December 14, 2008.

Background— Despite widespread clinical use as a prognostic marker in ischemic heart disorders, the actual pathogenetic role of the short pentraxin, C-reactive protein, has not undergone stringent genetic testing because of evolutionary divergence between mouse and humans. The long pentraxin PTX3 is conserved in evolution, is expressed in the heart under inflammatory conditions, and is a candidate prognostic marker in acute myocardial infarction. It was therefore important to assess whether PTX3 plays a pathogenetic role in acute myocardial infarction.

Methods and Results— In a model of acute myocardial infarction caused by coronary artery ligation and reperfusion, tissue mRNA expression and circulating levels of PTX3 increased. The interleukin-1R–MyD88 pathway plays a pivotal role in the induction of PTX3 transcript after ischemia. ptx3-deficient mice showed exacerbated heart damage (33% larger infarcts in null mice; P=0.0047). Increased myocardial damage in ptx3-deficient mice was associated with a greater no-reflow area, increased neutrophil infiltration, decreased number of capillaries, and increased number of apoptotic cardiomyocytes. In addition, ptx3-deficient mice with acute myocardial infarction showed higher circulating levels of interleukin-6 and increased C3 deposition in lesional tissue. The phenotype was reversed by exogenous PTX3.

Conclusions— Thus, PTX3 plays a nonredundant, regulatory, cardioprotective role in acute myocardial infarction in mice. Our results suggest that modulation of the complement cascade contributes to the cardioprotective function of PTX3.

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CLINICAL PERSPECTIVE

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Clinical Summaries
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