title: Loss of Macrophage Wnt Secretion Improves Remodeling and Function After Myocardial Infarction in Mice.
abstract: Macrophages and Wnt proteins (Wnts) are independently involved in cardiac development, response to cardiac injury, and repair. However, the role of macrophage-derived Wnts in the healing and repair of myocardial infarction (MI) is unknown. We sought to determine the role of macrophage Wnts in infarct repair.
  
  
  
  We show that the Wnt pathway is activated after MI in mice. Furthermore, we demonstrate that isolated infarct macrophages express distinct Wnt pathway components and are a source of noncanonical Wnts after MI. To determine the effect of macrophage Wnts on cardiac repair, we evaluated mice lacking the essential Wnt transporter Wntless (Wls) in myeloid cells. Significantly, Wntless-deficient macrophages presented a unique subset of M2-like macrophages with anti-inflammatory, reparative, and angiogenic properties. Serial echocardiography studies revealed that mice lacking macrophage Wnt secretion showed improved function and less remodeling 30 days after MI. Finally, mice lacking macrophage-Wntless had increased vascularization near the infarct site compared with controls.
  
  
  
  Macrophage-derived Wnts are implicated in adverse cardiac remodeling and dysfunction after MI. Together, macrophage Wnts could be a new therapeutic target to improve infarct healing and repair.
authors.affiliation: Neufeld Cardiac Research Institute, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.|Tamman Cardiovascular Research Institute, Leviev Heart Center, Sheba Medical Center, Tel-Hashomer, Israel.|Sheba Center for Regenerative Medicine, Stem Cells and Tissue Engineering, Tel-Hashomer, Israel.
authors.forename: Dahlia
authors.initials: D
authors.lastname: Palevski
authors.affiliation: Neufeld Cardiac Research Institute, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.|Tamman Cardiovascular Research Institute, Leviev Heart Center, Sheba Medical Center, Tel-Hashomer, Israel.|Sheba Center for Regenerative Medicine, Stem Cells and Tissue Engineering, Tel-Hashomer, Israel.
authors.forename: La-Paz
authors.initials: LP
authors.lastname: Levin-Kotler
authors.affiliation: Neufeld Cardiac Research Institute, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.|Tamman Cardiovascular Research Institute, Leviev Heart Center, Sheba Medical Center, Tel-Hashomer, Israel.|Sheba Center for Regenerative Medicine, Stem Cells and Tissue Engineering, Tel-Hashomer, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Kain
authors.affiliation: Neufeld Cardiac Research Institute, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.|Tamman Cardiovascular Research Institute, Leviev Heart Center, Sheba Medical Center, Tel-Hashomer, Israel.|Sheba Center for Regenerative Medicine, Stem Cells and Tissue Engineering, Tel-Hashomer, Israel.
authors.forename: Nili
authors.initials: N
authors.lastname: Naftali-Shani
authors.affiliation: Neufeld Cardiac Research Institute, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.|Tamman Cardiovascular Research Institute, Leviev Heart Center, Sheba Medical Center, Tel-Hashomer, Israel.|Sheba Center for Regenerative Medicine, Stem Cells and Tissue Engineering, Tel-Hashomer, Israel.
authors.forename: Natalie
authors.initials: N
authors.lastname: Landa
authors.affiliation: Neufeld Cardiac Research Institute, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.|Tamman Cardiovascular Research Institute, Leviev Heart Center, Sheba Medical Center, Tel-Hashomer, Israel.|Sheba Center for Regenerative Medicine, Stem Cells and Tissue Engineering, Tel-Hashomer, Israel.
authors.forename: Tammy
authors.initials: T
authors.lastname: Ben-Mordechai
authors.affiliation: Neufeld Cardiac Research Institute, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.|Tamman Cardiovascular Research Institute, Leviev Heart Center, Sheba Medical Center, Tel-Hashomer, Israel.|Sheba Center for Regenerative Medicine, Stem Cells and Tissue Engineering, Tel-Hashomer, Israel.
authors.forename: Tal
authors.initials: T
authors.lastname: Konfino
authors.affiliation: Neufeld Cardiac Research Institute, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.|Tamman Cardiovascular Research Institute, Leviev Heart Center, Sheba Medical Center, Tel-Hashomer, Israel.|Sheba Center for Regenerative Medicine, Stem Cells and Tissue Engineering, Tel-Hashomer, Israel.
authors.forename: Radka
authors.initials: R
authors.lastname: Holbova
authors.affiliation: Neufeld Cardiac Research Institute, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.|Tamman Cardiovascular Research Institute, Leviev Heart Center, Sheba Medical Center, Tel-Hashomer, Israel.|Sheba Center for Regenerative Medicine, Stem Cells and Tissue Engineering, Tel-Hashomer, Israel.
authors.forename: Natali
authors.initials: N
authors.lastname: Molotski
authors.affiliation: Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Rina
authors.initials: R
authors.lastname: Rosin-Arbesfeld
authors.affiliation: The Visual Systems Group Divisions of Pediatric Ophthalmology and Developmental Biology, Cincinnati Children's Hospital Medical Center Research Foundation, Cincinnati, OH.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lang
authors.affiliation: Neufeld Cardiac Research Institute, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel leorj@post.tau.ac.il.|Tamman Cardiovascular Research Institute, Leviev Heart Center, Sheba Medical Center, Tel-Hashomer, Israel.|Sheba Center for Regenerative Medicine, Stem Cells and Tissue Engineering, Tel-Hashomer, Israel.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Leor
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004452:Echocardiography; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D009203:Myocardial Infarction / Q000000981:diagnostic imaging* / Q000276:immunology; D018919:Neovascularization, Physiologic / Q000235:genetics* / Q000276:immunology; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D020257:Ventricular Remodeling / Q000235:genetics* / Q000276:immunology; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway
chemical_list: C545200:Gpr177 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; D051153:Wnt Proteins
keywords: Wnt signaling; macrophage; myocardial infarction; remodeling