The evolving cardiac lymphatic vasculature in development, repair and regeneration.
The evolving cardiac lymphatic vasculature in development, repair and regeneration.
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DOI：
10.1038/s41569-020-00489-x
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发表时间：
2021-05
期刊：
影响因子：
--
通讯作者：
Riley PR
中科院分区：
文献类型：
--
作者：
Klaourakis K;Vieira JM;Riley PR
淋巴管系统在维持组织中的正常液体平衡和调节对损伤或病原体的炎症反应中起重要作用。淋巴管正常发育或功能的破坏可能会产生严重的后果。在心脏中，淋巴功能降低可导致心肌水肿和持续性炎症。巨噬细胞是先天免疫系统的吞噬细胞，有助于心脏发育和心肌梗死后心脏组织的纤维化修复和再生。在这篇综述中，我们讨论了心脏淋巴管系统的重点发展，在过去5年中所产生的哺乳动物和斑马鱼模式生物的研究。此外，我们还研究了心肌梗死后纤维化修复和再生过程中心肌细胞和巨噬细胞之间的相互作用。最后，我们讨论了靶向心脏淋巴网络调节免疫细胞含量和减轻缺血性心脏病患者炎症的治疗潜力。本文综述了心脏淋巴管的发育、结构和功能的最新研究进展，探讨了心脏淋巴管在心肌损伤后纤维化修复和再生过程中的作用，并重点介绍了以心脏淋巴管为靶点治疗心肌梗死的潜力。心脏淋巴管系统在胚胎发育期间出现，并在结构和功能上继续成熟，直到出生后晚期。静脉和非静脉来源都有助于心脏的淋巴管内皮，静脉来源的淋巴管内皮细胞的身份在胚胎中胚层特化过程中的发育早期就被确定。在成年小鼠中，心肌细胞对心脏损伤的反应是在受损区域内发芽，试图清除免疫细胞和多余的组织液（水肿）。药物诱导的淋巴对损伤反应的增强改善了成年小鼠的心脏修复和功能，这表明该药物可能是心肌梗死和其他疾病的可能药物靶点。新生小鼠心脏具有再生能力，需要存在促修复巨噬细胞，这表明在新生心脏再生期间心脏再生剂的替代功能。成年斑马鱼可以在冷冻损伤后再生心脏，并且这些细胞对损伤部位做出反应，以清除浸润的免疫细胞，这是完全再生所必需的过程。
The lymphatic vasculature has an essential role in maintaining normal fluid balance in tissues and modulating the inflammatory response to injury or pathogens. Disruption of normal development or function of lymphatic vessels can have severe consequences. In the heart, reduced lymphatic function can lead to myocardial oedema and persistent inflammation. Macrophages, which are phagocytic cells of the innate immune system, contribute to cardiac development and to fibrotic repair and regeneration of cardiac tissue after myocardial infarction. In this Review, we discuss the cardiac lymphatic vasculature with a focus on developments over the past 5 years arising from the study of mammalian and zebrafish model organisms. In addition, we examine the interplay between the cardiac lymphatics and macrophages during fibrotic repair and regeneration after myocardial infarction. Finally, we discuss the therapeutic potential of targeting the cardiac lymphatic network to regulate immune cell content and alleviate inflammation in patients with ischaemic heart disease. This Review summarizes the latest knowledge on cardiac lymphatic development, structure and function, discusses the role of the cardiac lymphatics after myocardial injury during fibrotic repair and regeneration, and highlights the therapeutic potential of targeting the cardiac lymphatics in myocardial infarction. The cardiac lymphatic vasculature appears during embryonic development and continues to mature structurally and functionally until late postnatal stages. Both venous and non-venous sources contribute to the lymphatic endothelium of the heart, and the identity of the lymphatic endothelial cells of venous origin is defined very early in development during specification of the embryonic mesoderm. In adult mice, the cardiac lymphatics respond to cardiac injury by sprouting within the damaged area in an attempt to clear the immune cells and excess tissue fluid (oedema). Drug-induced augmentation of the lymphatic response to injury improves heart repair and function in adult mice, suggesting that the lymphatics could be a possible drug target for myocardial infarction and for other diseases. The neonatal mouse heart has regenerative capacity that requires the presence of pro-reparative macrophages, which suggests an alternative function for the cardiac lymphatics during neonatal heart regeneration. Adult zebrafish can regenerate their heart after cryoinjury, and the lymphatics respond to the site of injury to clear infiltrating immune cells, a process that is essential for complete regeneration.
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