Wnt5a-Mediated Neutrophil Recruitment Has an Obligatory Role in Pressure Overload-Induced Cardiac Dysfunction.
Wnt5a-Mediated Neutrophil Recruitment Has an Obligatory Role in Pressure Overload-Induced Cardiac Dysfunction.
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DOI：
10.1161/circulationaha.118.038820
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发表时间：
2019-08
期刊：
影响因子：
37.8
通讯作者：
Ying Wang;S. Sano;Kosei Oshima;Miho Sano;Yosuke Watanabe;Y. Katanasaka;Yoshimitsu Yura;Changhee Jung-Cha
中科院分区：
文献类型：
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作者：
Ying Wang;S. Sano;Kosei Oshima;Miho Sano;Yosuke Watanabe;Y. Katanasaka;Yoshimitsu Yura;Changhee Jung-Cha
背景虽然巨噬细胞在心肌损伤中的复杂作用已被广泛认识，但中性粒细胞在非缺血性心脏病理学中的功能受到的关注相对较少。方法 为了检查中性粒细胞在压力超负荷诱导的心脏肥大中的调节和功能，小鼠接受 Ly6G 抗体处理以消耗中性粒细胞，然后进行横主动脉缩窄 (TAC)。结果 中性粒细胞消耗减少了 TAC 引起的肥大和炎症，并保留了心脏功能。 Wnt5a（一种非典型 Wnt）的骨髓缺陷抑制了 TAC 治疗小鼠心脏的中性粒细胞浸润，并产生了与中性粒细胞减少状况相似的表型。相反，骨髓细胞过度表达 Wnt5a 的小鼠表现出更大的肥大性生长、炎症和心脏功能障碍。中性粒细胞耗竭逆转了 Wnt5a 过度表达诱导的心脏病理学，并消除了野生型和骨髓特异性 Wnt5a 转基因小鼠之间心脏参数的差异。结论 这些发现表明，Wnt5a 调节的中性粒细胞浸润在压力超负荷诱发的心力衰竭中具有关键作用。
BACKGROUND While the complex roles of macrophages in myocardial injury is widely appreciated, the function of neutrophils in non-ischemic cardiac pathology has received relatively little attention. METHODS To examine the regulation and function of neutrophils in pressure overload-induced cardiac hypertrophy, mice underwent treatment with Ly6G antibody to deplete neutrophils and then subjected to transverse aortic constriction (TAC). RESULTS Neutrophil depletion diminished TAC-induced hypertrophy and inflammation, and preserved cardiac function. Myeloid deficiency of Wnt5a, a non-canonical Wnt, suppressed neutrophil infiltration to the hearts of TAC-treated mice and produced a phenotype that was similar to the neutropenic conditions. Conversely, mice overexpressing Wnt5a in myeloid cells displayed greater hypertrophic growth, inflammation and cardiac dysfunction. Neutrophil depletion reversed the Wnt5a overexpression-induced cardiac pathology and eliminated differences in cardiac parameters between wild-type and myeloid-specific Wnt5a transgenic mice. CONCLUSIONS These findings reveal that Wnt5a-regulated neutrophil infiltration has a critical role in pressure overload-induced heart failure.