期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 115, 期 35, 页码 8805-8810出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1722594115
关键词
heart; vegfa; angiogenesis; regeneration
资金
- National Institutes of Health (NIH) Mentored Clinical Scientist Award [K08-HL116485]
- NIH Predoctoral Fellowship Award [F30 HL126487]
- NIH [R01-HL081674, R01-HL131319]
- March of Dimes Grant [1-FY14-205]
- Walker P. Inman Endowment
- Edna and Fred L. Mandel Foundation
- American Heart Association Merit Award [16MERIT27940012]
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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