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Coronary Revascularization During Heart Regeneration Is Regulated by Epicardial and Endocardial Cues and Forms a Scaffold for Cardiomyocyte Repopulation.
- Source :
-
Developmental cell [Dev Cell] 2019 Nov 18; Vol. 51 (4), pp. 503-515.e4. - Publication Year :
- 2019
-
Abstract
- 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.<br /> (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Cell Proliferation physiology
Chemokine CXCL12 metabolism
Cues
Endocardium physiology
Heart physiology
Heart Ventricles metabolism
Myocardial Revascularization methods
Myocytes, Cardiac metabolism
Pericardium physiology
Receptors, CXCR4 metabolism
Signal Transduction physiology
Wound Healing physiology
Zebrafish metabolism
Zebrafish Proteins metabolism
Myocytes, Cardiac physiology
Neovascularization, Physiologic physiology
Regeneration physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1551
- Volume :
- 51
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Developmental cell
- Publication Type :
- Academic Journal
- Accession number :
- 31743664
- Full Text :
- https://doi.org/10.1016/j.devcel.2019.10.019