RRC ID 87784
Author Marín-Juez R, El-Sammak H, Helker CSM, Kamezaki A, Mullapuli ST, Bibli SI, Foglia MJ, Fleming I, Poss KD, Stainier DYR.
Title Coronary Revascularization During Heart Regeneration Is Regulated by Epicardial and Endocardial Cues and Forms a Scaffold for Cardiomyocyte Repopulation.
Journal Dev Cell
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.
Volume 51(4)
Pages 503-515.e4
Published 2019-11-18
DOI 10.1016/j.devcel.2019.10.019
PII S1534-5807(19)30866-4
PMID 31743664
PMC PMC6982407
MeSH 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
IF 10.092
Resource
Medaka tg1206