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  Fast revascularization of the injured area is essential to support zebrafish heart regeneration

Marin-Juez, R., Marass, M., Gauvrit, S., Rossi, A., Lai, S.-L., Materna, S. C., et al. (2016). Fast revascularization of the injured area is essential to support zebrafish heart regeneration. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 113(40), 11237-11242. doi:10.1073/pnas.1605431113.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0001-BD52-E Version Permalink: http://hdl.handle.net/21.11116/0000-0007-459E-A
Genre: Journal Article

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 Creators:
Marin-Juez, Ruben1, Author              
Marass, Michele1, Author              
Gauvrit, Sebastien1, Author              
Rossi, Andrea1, Author              
Lai, Shih-Lei1, Author              
Materna, Stefan C., Author
Black, Brian L., Author
Stainier, Didier Y.R.1, Author              
Affiliations:
1Developmental Genetics, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591697              

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Free keywords: ENDOTHELIAL-GROWTH-FACTOR; EMBRYONIC LYMPHANGIOGENESIS; MYOCARDIAL-INFARCTION; VASCULAR DEVELOPMENT; CELLS; ANGIOGENESIS; REVEALS; CARDIOMYOCYTES; EPICARDIUM; ARTERIESScience & Technology - Other Topics; heart regeneration; angiogenesis; revascularization; coronaries; VEGF;
 Abstract: Zebrafish have a remarkable capacity to regenerate their heart. Efficient replenishment of lost tissues requires the activation of different cell types including the epicardium and endocardium. A complex set of processes is subsequently needed to support cardiomyocyte repopulation. Previous studies have identified important determinants of heart regeneration; however, to date, how revascularization of the damaged area happens remains unknown. Here, we show that angiogenic sprouting into the injured area starts as early as 15 h after injury. To analyze the role of vegfaa in heart regeneration, we used vegfaa mutants rescued to adulthood by vegfaa mRNA injections at the one-cell stage. Surprisingly, vegfaa mutants develop coronaries and revascularize after injury. As a possible explanation for these observations, we find that vegfaa mutant hearts up-regulate the expression of potentially compensating genes. Therefore, to overcome the lack of a revascularization phenotype in vegfaa mutants, we generated fish expressing inducible dominant negative Vegfaa. These fish displayed minimal revascularization of the damaged area. In the absence of fast angiogenic revascularization, cardiomyocyte proliferation did not occur, and the heart failed to regenerate, retaining a fibrotic scar. Hence, our data show that a fast endothelial invasion allows efficient revascularization of the injured area, which is necessary to support replenishment of new tissue and achieve efficient heart regeneration. These findings revisit the model where neovascularization is considered to happen concomitant with the formation of new muscle. Our work also paves the way for future studies designed to understand the molecular mechanisms that regulate fast revascularization.

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Language(s): eng - English
 Dates: 2016
 Publication Status: Published in print
 Pages: 6
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000384528900062
DOI: 10.1073/pnas.1605431113
 Degree: -

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Title: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Source Genre: Journal
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Publ. Info: 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA : NATL ACAD SCIENCES
Pages: - Volume / Issue: 113 (40) Sequence Number: - Start / End Page: 11237 - 11242 Identifier: ISSN: 0027-8424