Loss of macrophage Wnt secretion improves remodeling and function after myocardial infarction in mice

Dahlia Palevski, La Paz Levin-Kotler, David Kain, Nili Naftali-Shani, Natalie Landa, Tammy Ben-Mordechai, Tal Konfino, Radka Holbova, Natali Molotski, Rina Rosin-Arbesfeld, Richard A. Lang, Jonathan Leor*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

58 Scopus citations


Background--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. Methods and Results--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. Conclusions--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.

Original languageEnglish
Article numbere004387
JournalJournal of the American Heart Association
Issue number1
StatePublished - 2017


  • Macrophage
  • Myocardial infarction
  • Remodeling
  • Wnt signaling


Dive into the research topics of 'Loss of macrophage Wnt secretion improves remodeling and function after myocardial infarction in mice'. Together they form a unique fingerprint.

Cite this