PMID- 21836067 OWN - NLM STAT- MEDLINE DCOM- 20120123 LR - 20201209 IS - 1524-4636 (Electronic) IS - 1079-5642 (Linking) VI - 31 IP - 11 DP - 2011 Nov TI - Secreted frizzled-related protein-1 improves postinfarction scar formation through a modulation of inflammatory response. PG - e80-7 LID - 10.1161/ATVBAHA.111.232280 [doi] AB - 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. METHODS AND 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. CONCLUSION: 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. FAU - Barandon, Laurent AU - Barandon L AD - Universite de Bordeaux, Adaptation Cardiovasculaire a l'ischemie, U1034, Pessac, France. FAU - Casassus, Frederic AU - Casassus F FAU - Leroux, Lionel AU - Leroux L FAU - Moreau, Catherine AU - Moreau C FAU - Allieres, Cecile AU - Allieres C FAU - Lamaziere, Jean-Marie Daniel AU - Lamaziere JM FAU - Dufourcq, Pascale AU - Dufourcq P FAU - Couffinhal, Thierry AU - Couffinhal T FAU - Duplaa, Cecile AU - Duplaa C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Arterioscler Thromb Vasc Biol JT - Arteriosclerosis, thrombosis, and vascular biology JID - 9505803 RN - 0 (Cytokines) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Proteins) RN - 0 (WD repeat containing planar cell polarity effector) SB - IM MH - Animals MH - Bone Marrow Cells/metabolism/pathology MH - Bone Marrow Transplantation MH - Cell Line MH - Cell Movement/physiology MH - Cell Proliferation MH - Cells, Cultured MH - Cicatrix/*etiology/*metabolism/pathology MH - Cytokines/metabolism MH - Endothelium, Vascular/metabolism/pathology MH - Humans MH - In Vitro Techniques MH - Inflammation/*metabolism MH - Intracellular Signaling Peptides and Proteins MH - Mice MH - Mice, Transgenic MH - Models, Animal MH - Myocardial Infarction/*complications/*metabolism MH - Myocytes, Cardiac/metabolism/pathology MH - Neutrophils/drug effects/pathology MH - Proteins/*metabolism/pharmacology EDAT- 2011/08/13 06:00 MHDA- 2012/01/24 06:00 CRDT- 2011/08/13 06:00 PHST- 2011/08/13 06:00 [entrez] PHST- 2011/08/13 06:00 [pubmed] PHST- 2012/01/24 06:00 [medline] AID - ATVBAHA.111.232280 [pii] AID - 10.1161/ATVBAHA.111.232280 [doi] PST - ppublish SO - Arterioscler Thromb Vasc Biol. 2011 Nov;31(11):e80-7. doi: 10.1161/ATVBAHA.111.232280.