ZFIN ID: ZDB-PUB-191120-11
Coronary Revascularization During Heart Regeneration Is Regulated by Epicardial and Endocardial Cues and Forms a Scaffold for Cardiomyocyte Repopulation
Marín-Juez, R., El-Sammak, H., Helker, C.S.M., Kamezaki, A., Mullapuli, S.T., Bibli, S.I., Foglia, M.J., Fleming, I., Poss, K.D., Stainier, D.Y.R.
Date: 2019
Source: Developmental Cell   51: 503-515.e4 (Journal)
Registered Authors: Foglia, Matthew, Helker, Christian, Marín-Juez, Rubén, Poss, Kenneth D., Stainier, Didier
Keywords: Apelin, Cxcl12/Cxcr4, Vegfa, coronaries, endocardium, epicardium, heart regeneration, hypoxia, revascularization, zebrafish
MeSH Terms:
  • Animals
  • Cell Proliferation/physiology
  • Chemokine CXCL12/metabolism
  • Cues
  • Endocardium/physiology
  • Heart/physiology
  • Heart Ventricles/metabolism
  • Myocardial Revascularization/methods
  • Myocytes, Cardiac/metabolism
  • Myocytes, Cardiac/physiology*
  • Neovascularization, Physiologic/physiology*
  • Pericardium/physiology
  • Receptors, CXCR4/metabolism
  • Regeneration/physiology*
  • Signal Transduction/physiology
  • Wound Healing/physiology
  • Zebrafish/metabolism
  • Zebrafish Proteins/metabolism
PubMed: 31743664 Full text @ Dev. Cell
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.