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Vegfaa instructs cardiac muscle hyperplasia in adult zebrafish.

Publication ,  Journal Article
Karra, R; Foglia, MJ; Choi, W-Y; Belliveau, C; DeBenedittis, P; Poss, KD
Published in: Proc Natl Acad Sci U S A
August 28, 2018

During heart development and regeneration, coronary vascularization is tightly coupled with cardiac growth. Although inhibiting vascularization causes defects in the innate regenerative response of zebrafish to heart injury, angiogenic signals are not known to be sufficient for triggering regeneration events. Here, by using a transgenic reporter strain, we found that regulatory sequences of the angiogenic factor vegfaa are active in epicardial cells of uninjured animals, as well as in epicardial and endocardial tissue adjacent to regenerating muscle upon injury. Additionally, we find that induced cardiac overexpression of vegfaa in zebrafish results in overt hyperplastic thickening of the myocardial wall, accompanied by indicators of angiogenesis, epithelial-to-mesenchymal transition, and cardiomyocyte regeneration programs. Unexpectedly, vegfaa overexpression in the context of cardiac injury enabled ectopic cardiomyogenesis but inhibited regeneration at the site of the injury. Our findings identify Vegfa as one of a select few known factors sufficient to activate adult cardiomyogenesis, while also illustrating how instructive factors for heart regeneration require spatiotemporal control for efficacy.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

August 28, 2018

Volume

115

Issue

35

Start / End Page

8805 / 8810

Location

United States

Related Subject Headings

  • Zebrafish Proteins
  • Zebrafish
  • Vascular Endothelial Growth Factor A
  • Myocytes, Cardiac
  • Myocardium
  • Hyperplasia
  • Epithelial-Mesenchymal Transition
  • Cardiomegaly
  • Animals
 

Citation

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Karra, R., Foglia, M. J., Choi, W.-Y., Belliveau, C., DeBenedittis, P., & Poss, K. D. (2018). Vegfaa instructs cardiac muscle hyperplasia in adult zebrafish. Proc Natl Acad Sci U S A, 115(35), 8805–8810. https://doi.org/10.1073/pnas.1722594115
Karra, Ravi, Matthew J. Foglia, Wen-Yee Choi, Christine Belliveau, Paige DeBenedittis, and Kenneth D. Poss. “Vegfaa instructs cardiac muscle hyperplasia in adult zebrafish.Proc Natl Acad Sci U S A 115, no. 35 (August 28, 2018): 8805–10. https://doi.org/10.1073/pnas.1722594115.
Karra R, Foglia MJ, Choi W-Y, Belliveau C, DeBenedittis P, Poss KD. Vegfaa instructs cardiac muscle hyperplasia in adult zebrafish. Proc Natl Acad Sci U S A. 2018 Aug 28;115(35):8805–10.
Karra, Ravi, et al. “Vegfaa instructs cardiac muscle hyperplasia in adult zebrafish.Proc Natl Acad Sci U S A, vol. 115, no. 35, Aug. 2018, pp. 8805–10. Pubmed, doi:10.1073/pnas.1722594115.
Karra R, Foglia MJ, Choi W-Y, Belliveau C, DeBenedittis P, Poss KD. Vegfaa instructs cardiac muscle hyperplasia in adult zebrafish. Proc Natl Acad Sci U S A. 2018 Aug 28;115(35):8805–8810.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

August 28, 2018

Volume

115

Issue

35

Start / End Page

8805 / 8810

Location

United States

Related Subject Headings

  • Zebrafish Proteins
  • Zebrafish
  • Vascular Endothelial Growth Factor A
  • Myocytes, Cardiac
  • Myocardium
  • Hyperplasia
  • Epithelial-Mesenchymal Transition
  • Cardiomegaly
  • Animals