A Unique Collateral Artery Development Program Promotes Neonatal Heart Regeneration
A Unique Collateral Artery Development Program Promotes Neonatal Heart Regeneration
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DOI：
10.1016/j.cell.2018.12.023
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发表时间：
2019-02-21
期刊：
影响因子：
64.5
通讯作者：
Red-Horse, Kristy
中科院分区：
文献类型：
--
作者：
Das, Soumyashree;Goldstone, Andrew B.;Red-Horse, Kristy
侧支动脉是一种不常见的血管亚型，可在血管闭塞后提供备用血流以保存组织。一些心脏病患者会出现冠状动脉侧支，这与生存率的增加有关。然而，目前还不知道这些侧枝是如何发育的，也不知道如何刺激它们。我们证明了新生小鼠心脏使用一种新的机制来建立侧支动脉以应对损伤。动脉内皮细胞（EC）从动脉沿着已有的毛细血管迁移并重新组装成侧支动脉，我们称之为“动脉重组”。动脉内皮细胞表达CXCR4，损伤后，毛细血管内皮细胞诱导其配体CXCL12。CXCL12或CXCR4缺失损害侧支动脉形成和新生儿心脏再生。动脉重组在成人中几乎不存在，但由外源性CXCL12诱导。因此，了解新生儿再生机制可以确定恢复成人这些过程的途径，并确定缺血性心脏病的潜在治疗策略。
Collateral arteries are an uncommon vessel subtype that can provide alternate blood flow to preserve tissue following vascular occlusion. Some patients with heart disease develop collateral coronary arteries, and this correlates with increased survival. However, it is not known how these collaterals develop or how to stimulate them. We demonstrate that neonatal mouse hearts use a novel mechanism to build collateral arteries in response to injury. Arterial endothelial cells (ECs) migrated away from arteries along existing capillaries and reassembled into collateral arteries, which we termed "artery reassembly''. Artery ECs expressed CXCR4, and following injury, capillary ECs induced its ligand, CXCL12. CXCL12 or CXCR4 deletion impaired collateral artery formation and neonatal heart regeneration. Artery reassembly was nearly absent in adults but was induced by exogenous CXCL12. Thus, understanding neonatal regenerative mechanisms can identify pathways that restore these processes in adults and identify potentially translatable therapeutic strategies for ischemic heart disease.