期刊
JOURNAL OF THE AMERICAN HEART ASSOCIATION
卷 6, 期 1, 页码 -出版社
WILEY-BLACKWELL
DOI: 10.1161/JAHA.116.004387
关键词
macrophage; myocardial infarction; remodeling; Wnt signaling
资金
- Cincinnati Children's Hospital-Tel Aviv University Joint Research Grant
- Cincinnati Children's Hospital-Sheba Medical Center Joint Research Grant
- Seymour Fefer Research Grant
- Lev Heart Center
- Sheba Medical Center
- Israeli Science Foundation [10/14]
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.
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