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首页> 外文期刊>Circulation journal >Expanding role of delta-like 4 mediated notch signaling in cardiovascular and metabolic diseases
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Expanding role of delta-like 4 mediated notch signaling in cardiovascular and metabolic diseases

机译：δ样4介导的Notch信号在心血管和代谢疾病中的扩展作用

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Cardiometabolic disease, a global health threat, has been linked to chronic inflammation, in which activated macro-phages play a key role. Macrophages are highly heterogeneous hematopoietic cells found in nearly every tissue in the body. Various stimuli recruit monocytes into the cardiovascular system and metabolic organs, where they differentiate to macrophages, and activate these pro-inflammatory phagocytes, leading to the initiation and development of inflammation in these organs. Key regulators of macrophage activation therefore may serve as therapeutic targets for cardiometabolic disease. The Notch signaling pathway, involving 5 ligands and 4 receptors, regulates the differentiation of various cell types during development, and also contributes to the disease processes in adults. We found that the Notch ligand delta-like 4 (Dll4) activates macrophages in vitro as determined by the induction of genes and pathways associated with cardiovascular and metabolic disorders. Our recent study demonstrated in vivo that blockade of Dll4 by a neutralizing antibody attenuates key features typical of cardiovascular and metabolic diseases, such as accumulation of activated macrophages in arteries and fat; chronic atherosclerosis; arterial and valvular calcification; insulin resistance; and fatty liver. These results suggest that Dll4-mediated Notch signaling participates in the shared disease mechanisms for cardiovascular and metabolic disorders. This review summarizes the role of macrophages and Dll4/Notch signaling in the development of inflammation in both the cardiovascular system and metabolic organs.
机译：心血管疾病是一种全球性健康威胁，已与慢性炎症相关，在慢性炎症中，活化的巨噬细胞起关键作用。巨噬细胞是在体内几乎所有组织中发现的高度异质的造血细胞。各种刺激将单核细胞募集到心血管系统和代谢器官中，在那里它们分化为巨噬细胞，并激活这些促炎性吞噬细胞，从而导致这些器官炎症的发生和发展。因此，巨噬细胞活化的关键调节剂可以作为心脏代谢疾病的治疗靶标。 Notch信号通路涉及5个配体和4个受体，可调节发育过程中各种细胞类型的分化，并且也有助于成年人的疾病进程。我们发现Notch配体δ样4（Dll4）在体外激活巨噬细胞，这是由与心血管疾病和代谢性疾病相关的基因和途径的诱导确定的。我们最近的研究在体内证明，通过中和抗体阻断Dll4可减弱心血管和代谢性疾病的典型特征，例如活化的巨噬细胞在动脉和脂肪中的积聚。慢性动脉粥样硬化动脉和瓣膜钙化;胰岛素抵抗;和脂肪肝。这些结果表明，Dll4介导的Notch信号参与了心血管和代谢疾病的共同疾病机制。这篇综述总结了巨噬细胞和Dll4 / Notch信号在心血管系统和代谢器官发炎中的作用。

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