Loss of Macrophage Wnt Secretion Improves Remodeling and Function After Myocardial Infarction in Mice.
Loss of Macrophage Wnt Secretion Improves Remodeling and Function After Myocardial Infarction in Mice.
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DOI：
10.1161/jaha.116.004387
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发表时间：
2017-01-06
影响因子：
5.4
通讯作者：
Leor J
中科院分区：
文献类型：
--
作者：
Palevski D;Levin-Kotler LP;Kain D;Naftali-Shani N;Landa N;Ben-Mordechai T;Konfino T;Holbova R;Molotski N;Rosin-Arbesfeld R;Lang RA;Leor J
巨噬细胞和 Wnt 蛋白 (Wnts) 独立参与心脏发育、心脏损伤反应和修复。然而，巨噬细胞衍生的 Wnt 在心肌梗死 (MI) 愈合和修复中的作用尚不清楚。我们试图确定巨噬细胞 Wnts 在梗塞修复中的作用。我们发现小鼠 MI 后 Wnt 通路被激活。此外，我们证明分离的梗死巨噬细胞表达不同的 Wnt 通路成分，并且是 MI 后非典型 Wnt 的来源。为了确定巨噬细胞 Wnts 对心脏修复的影响，我们评估了骨髓细胞中缺乏必需 Wnt 转运蛋白 Wntless (Wls) 的小鼠。值得注意的是，Wntless 缺陷型巨噬细胞呈现出独特的 M2 样巨噬细胞子集，具有抗炎、修复和血管生成特性。系列超声心动图研究表明，缺乏巨噬细胞 Wnt 分泌的小鼠在 MI 后 30 天表现出功能改善和重构减少。最后，与对照组相比，缺乏巨噬细胞-Wntless 的小鼠梗塞部位附近的血管化增加。巨噬细胞衍生的 Wnt 与 MI 后的不良心脏重塑和功能障碍有关。总之，巨噬细胞 Wnts 可能成为改善梗塞愈合和修复的新治疗靶点。
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. 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. 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.