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

Publication ,  Journal Article
Marín-Juez, R; El-Sammak, H; Helker, CSM; Kamezaki, A; Mullapuli, ST; Bibli, S-I; Foglia, MJ; Fleming, I; Poss, KD; Stainier, DYR
Published in: Dev Cell
November 18, 2019

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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Published In

Dev Cell

DOI

EISSN

1878-1551

Publication Date

November 18, 2019

Volume

51

Issue

4

Start / End Page

503 / 515.e4

Location

United States

Related Subject Headings

  • Zebrafish Proteins
  • Zebrafish
  • Wound Healing
  • Signal Transduction
  • Regeneration
  • Receptors, CXCR4
  • Pericardium
  • Neovascularization, Physiologic
  • Myocytes, Cardiac
  • Myocardial Revascularization
 

Citation

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Marín-Juez, R., El-Sammak, H., Helker, C. S. M., Kamezaki, A., Mullapuli, S. T., Bibli, S.-I., … Stainier, D. Y. R. (2019). Coronary Revascularization During Heart Regeneration Is Regulated by Epicardial and Endocardial Cues and Forms a Scaffold for Cardiomyocyte Repopulation. Dev Cell, 51(4), 503-515.e4. https://doi.org/10.1016/j.devcel.2019.10.019
Marín-Juez, Rubén, Hadil El-Sammak, Christian S. M. Helker, Aosa Kamezaki, Sri Teja Mullapuli, Sofia-Iris Bibli, Matthew J. Foglia, Ingrid Fleming, Kenneth D. Poss, and Didier Y. R. Stainier. “Coronary Revascularization During Heart Regeneration Is Regulated by Epicardial and Endocardial Cues and Forms a Scaffold for Cardiomyocyte Repopulation.Dev Cell 51, no. 4 (November 18, 2019): 503-515.e4. https://doi.org/10.1016/j.devcel.2019.10.019.
Marín-Juez R, El-Sammak H, Helker CSM, Kamezaki A, Mullapuli ST, Bibli S-I, et al. Coronary Revascularization During Heart Regeneration Is Regulated by Epicardial and Endocardial Cues and Forms a Scaffold for Cardiomyocyte Repopulation. Dev Cell. 2019 Nov 18;51(4):503-515.e4.
Marín-Juez, Rubén, et al. “Coronary Revascularization During Heart Regeneration Is Regulated by Epicardial and Endocardial Cues and Forms a Scaffold for Cardiomyocyte Repopulation.Dev Cell, vol. 51, no. 4, Nov. 2019, pp. 503-515.e4. Pubmed, doi:10.1016/j.devcel.2019.10.019.
Marín-Juez R, El-Sammak H, Helker CSM, Kamezaki A, Mullapuli ST, Bibli S-I, Foglia MJ, Fleming I, Poss KD, Stainier DYR. Coronary Revascularization During Heart Regeneration Is Regulated by Epicardial and Endocardial Cues and Forms a Scaffold for Cardiomyocyte Repopulation. Dev Cell. 2019 Nov 18;51(4):503-515.e4.
Journal cover image

Published In

Dev Cell

DOI

EISSN

1878-1551

Publication Date

November 18, 2019

Volume

51

Issue

4

Start / End Page

503 / 515.e4

Location

United States

Related Subject Headings

  • Zebrafish Proteins
  • Zebrafish
  • Wound Healing
  • Signal Transduction
  • Regeneration
  • Receptors, CXCR4
  • Pericardium
  • Neovascularization, Physiologic
  • Myocytes, Cardiac
  • Myocardial Revascularization