title: Cardioprotective function of the long pentraxin PTX3 in acute myocardial infarction.
abstract: 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.
  
  
  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.
authors.affiliation: Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Salio
authors.forename: Stefano
authors.initials: S
authors.lastname: Chimenti
authors.forename: Noeleen
authors.initials: N
authors.lastname: De Angelis
authors.forename: Fabiola
authors.initials: F
authors.lastname: Molla
authors.forename: Virginia
authors.initials: V
authors.lastname: Maina
authors.forename: Manuela
authors.initials: M
authors.lastname: Nebuloni
authors.forename: Fabio
authors.initials: F
authors.lastname: Pasqualini
authors.forename: Roberto
authors.initials: R
authors.lastname: Latini
authors.forename: Cecilia
authors.initials: C
authors.lastname: Garlanda
authors.forename: Alberto
authors.initials: A
authors.lastname: Mantovani
mesh_terms: D000818:Animals; D002097:C-Reactive Protein / Q000235:genetics* / Q000378:metabolism*; D003176:Complement C3 / Q000378:metabolism; D004195:Disease Models, Animal; D007375:Interleukin-1; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009203:Myocardial Infarction / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology; D010641:Phenotype; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D003176:Complement C3; D007375:Interleukin-1; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000099153:Pentraxins