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

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. © 2017 the authors.