Coronary Revascularization During Heart Regeneration Is Regulated by Epicardial and Endocardial Cues and Forms a Scaffold for Cardiomyocyte Repopulation.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Marín-Juez, R; El-Sammak, H; Helker, CSM; Kamezaki, A; Mullapuli, ST; Bibli, S-I; Foglia, MJ; Fleming, I; Poss, KD; Stainier, DYR

Published Date

  • November 18, 2019

Published In

Volume / Issue

  • 51 / 4

Start / End Page

  • 503 - 515.e4

PubMed ID

  • 31743664

Pubmed Central ID

  • PMC6982407

Electronic International Standard Serial Number (EISSN)

  • 1878-1551

Digital Object Identifier (DOI)

  • 10.1016/j.devcel.2019.10.019


  • eng

Conference Location

  • United States