Journal
DEVELOPMENTAL CELL
Volume 51, Issue 4, Pages 503-+Publisher
CELL PRESS
DOI: 10.1016/j.devcel.2019.10.019
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Funding
- Max Planck Society
- DFG [394046768, SFB1366, 75732319, SFB834/3]
- Leducq Foundation
- NIH [R01 HL131319, R01 HL136182, R01 HL081674]
- American Heart Association
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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.
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