Open AccessLoss of Macrophage Wnt Secretion Improves Remodeling and Function After Myocardial Infarction in Mice
Author(s) -
Palevski Dahlia,
LevinKotler LaPaz,
Kain David,
NaftaliShani Nili,
Landa Natalie,
BenMordechai Tammy,
Konfino Tal,
Holbova Radka,
Molotski Natali,
RosinArbesfeld Rina,
Lang Richard A.,
Leor Jonathan
Publication year - 2017
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.116.004387
Subject(s) - wnt signaling pathway , macrophage , medicine , myocardial infarction , secretion , catenin , inflammation , microbiology and biotechnology , cancer research , biology , signal transduction , biochemistry , in vitro
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.