title: Secreted frizzled-related protein-1 improves postinfarction scar formation through a modulation of inflammatory response.
abstract: OBJECTIVE
  The inflammatory response after myocardial infarction plays a crucial role in the healing process. Lately, there is accumulating evidence that the Wnt/Frizzled pathway may play a distinct role in inflammation. We have shown that secreted frizzled-related protein-1 (sFRP-1) overexpression reduced postinfarction scar size, and we noticed a decrease in neutrophil infiltration in the ischemic tissue. We aimed to further elucidate the role of sFRP-1 in the postischemic inflammatory process.
  
  
  RESULTS
  We found that in vitro, sFRP-1 was able to block leukocyte activation and cytokine production. We transplanted bone marrow cells (BMCs) from transgenic mice overexpressing sFRP-1 into wild-type recipient mice and compared myocardial healing with that of mice transplanted with wild-type BMCs. These results were compared with those obtained in transgenic mice overexpressing sFRP-1 specifically in endothelial cells or in cardiomyocytes to better understand the spatiotemporal mechanism of the sFRP-1 effect. Our findings indicate that when overexpressed in the BMCs, but not in endothelial cells or cardiomyocytes, sFRP-1 was able to reduce neutrophil infiltration after ischemia, by switching the balance of pro- and antiinflammatory cytokine expression, leading to a reduction in scar formation and better cardiac hemodynamic parameters.
  
  
  CONCLUSIONS
  sFRP-1 impaired the loop of cytokine amplification and decreased neutrophil activation and recruitment into the scar, without altering the neutrophil properties. These data support the notion that sFRP-1 may be a novel antiinflammatory factor protecting the heart from damage after myocardial infarction.
authors.affiliation: Université de Bordeaux, Adaptation Cardiovasculaire à l'ischémie, U1034, Pessac, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Barandon
authors.forename: Fréderic
authors.initials: F
authors.lastname: Casassus
authors.forename: Lionel
authors.initials: L
authors.lastname: Leroux
authors.forename: Catherine
authors.initials: C
authors.lastname: Moreau
authors.forename: Cécile
authors.initials: C
authors.lastname: Allières
authors.forename: Jean-Marie Daniel
authors.initials: JM
authors.lastname: Lamazière
authors.forename: Pascale
authors.initials: P
authors.lastname: Dufourcq
authors.forename: Thierry
authors.initials: T
authors.lastname: Couffinhal
authors.forename: Cécile
authors.initials: C
authors.lastname: Duplàa
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D016026:Bone Marrow Transplantation; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002921:Cicatrix / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D009203:Myocardial Infarction / Q000150:complications* / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D011506:Proteins / Q000378:metabolism* / Q000494:pharmacology; D000099274:Frizzled-Related Proteins
chemical_list: D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D000099274:Frizzled-Related Proteins