Plasma levels of neuropeptide Y (NPY) are elevated in patients with acute myocardial infarction (AMI), but its role in AMI remains unclear, which was examined here in NPY wild-type/knockout (WT/KO) mice treated with/without exogenous NPY and its Y1 receptor antagonist (Y1Ra) BIBP 3226. We found that AMI mice lacking NPY developed more severe AMI than WT mice with worse cardiac dysfunction, progressive cardiac inflammation and fibrosis, and excessive apoptosis but impairing angiogenesis. All of these changes were reversed when the NPY KO mice were treated with exogenous NPY in a dose-dependent manner. Interestingly, treatment with NPY also dose dependently attenuated AMI in WT mice, which was blocked by BIBP 3226. Phenotypically, cardiac NPY was de novo expressed by infiltrating macrophages during the repairing or fibrosing process in heart-failure patients and AMI mice. Mechanistically, NPY was induced by transforming growth factor (TGF)-β1 in bone marrow-derived macrophages and signaled through its Y1R to exert its pathophysiological activities by inhibiting p38/nuclear factor κB (NF-κB)-mediated M1 macrophage activation while promoting the reparative M2 phenotype in vivo and in vitro. In conclusion, NPY can attenuate AMI in mice. Inhibition of cardiac inflammation and fibrosis while enhancing angiogenesis but reducing apoptosis may be the underlying mechanisms through which NPY attenuates cardiac remodeling and deterioration of function following AMI.

急性心肌梗死 (AMI) 患者的血浆神经肽 Y (NPY) 水平升高，但其在 AMI 中的作用仍不清楚，此处在用/不用外源性NPY 及其 Y1 受体拮抗剂 (Y1Ra) BIBP 3226。我们发现缺乏 NPY 的 AMI 小鼠比 WT 小鼠发展出更严重的 AMI，心脏功能障碍更严重，进行性心脏炎症和纤维化，细胞凋亡过多但会损害血管生成。当以剂量依赖性方式用外源性 NPY 处理 NPY KO 小鼠时，所有这些变化都会逆转。有趣的是，用 NPY 治疗还可以剂量依赖性地减轻 WT 小鼠的 AMI，这被 BIBP 3226 阻断了。表型上，心脏 NPY 在心力衰竭患者和 AMI 小鼠的修复或纤维化过程中通过浸润巨噬细胞从头表达。从机制上讲，NPY 由骨髓来源的巨噬细胞中的转化生长因子 (TGF)-β1 诱导，并通过其 Y1R 发出信号，通过抑制 p38/核因子 κB (NF-κB) 介导的 M1 巨噬细胞活化来发挥其病理生理活性，同时促进修复性 M2 表型体内和体外。总之，NPY 可以减轻小鼠的 AMI。抑制心脏炎症和纤维化同时增强血管生成但减少细胞凋亡可能是 NPY 减弱 AMI 后心脏重塑和功能恶化的潜在机制。