Defective coronary network function and insufficient blood supply are both cause and consequence of myocardial infarction. Efficient revascularization after infarction is essential to support tissue repair and function. Zebrafish hearts exhibit a remarkable ability to regenerate, and coronary revascularization initiates within hours of injury, but how this process is regulated remains unknown. Here, we show that revascularization requires a coordinated multi-tissue response culminating with the formation of a complex vascular network available as a scaffold for cardiomyocyte repopulation. During a process we term "coronary-endocardial anchoring," new coronaries respond by sprouting (1) superficially within the regenerating epicardium and (2) intra-ventricularly toward the activated endocardium. Mechanistically, superficial revascularization is guided by epicardial Cxcl12-Cxcr4 signaling and intra-ventricular sprouting by endocardial Vegfa signaling. Our findings indicate that the injury-activated epicardium and endocardium support cardiomyocyte replenishment initially through the guidance of coronary sprouting. Simulating this process in the injured mammalian heart should help its healing.

中文翻译：

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心脏再生期间的冠状动脉血运重建受心外膜和心内膜信号的调节，并形成心肌细胞再增殖的支架。

冠状动脉网络功能缺陷和供血不足是心肌梗塞的原因和后果。梗死后有效的血运重建对于支持组织修复和功能至关重要。斑马鱼心脏表现出非凡的再生能力，冠状动脉血运重建在受伤后数小时内开始，但如何调节这一过程仍然未知。在这里，我们表明血运重建需要协调的多组织反应，最终形成一个复杂的血管网络，可用作心肌细胞再增殖的支架。在我们称之为“冠状动脉-心内膜锚定”的过程中，新冠状动脉通过 (1) 在再生心外膜表面发芽和 (2) 在心室内朝向激活的心内膜发芽作出反应。机械地，表层血运重建由心外膜 Cxcl12-Cxcr4 信号传导和心内膜 Vegfa 信号传导心室内萌芽。我们的研究结果表明，损伤激活的心外膜和心内膜最初通过冠状动脉萌芽的指导支持心肌细胞的补充。在受伤的哺乳动物心脏中模拟这个过程应该有助于其愈合。