Key result
Mice lacking macrophage Wnt secretion showed improved cardiac function, less remodeling, and increased vascularization near the infarct site 30 days after myocardial infarction compared with controls.
Why the study?
Does deletion of Wnt transporter Wntless in myeloid cells improve remodeling and function after myocardial infarction in mice?
Does deletion of Wnt transporter Wntless in myeloid cells improve remodeling and function after myocardial infarction in mice?
Macrophage-derived Wnts contribute to adverse cardiac remodeling after MI, and their targeted inhibition may offer a novel therapeutic approach to improve infarct healing.
Preclinical MI data suggest macrophage Wnt targeting may aid repair; leaves open translation to human therapy.
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.
No takes yet. Share an insight, caveat, or question.
Palevski et al. (2017) studied Myocardial infarction. Deletion of Wntless (Wls) in myeloid cells vs. Controls was evaluated on Cardiac function and remodeling. Mice lacking macrophage Wnt secretion showed improved cardiac function, less remodeling, and increased vascularization near the infarct site 30 days after myocardial infarction compared with controls.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: