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Nature. 2015 Sep 24;525(7570):479-85. doi: 10.1038/nature15372. Epub 2015 Sep 16.

Epicardial FSTL1 reconstitution regenerates the adult mammalian heart.

Author information

1
Department of Bioengineering, University of California, San Diego, La Jolla, California 92037, USA.
2
Sanford-Burnham-Prebys Medical Discovery Institute, 10901 N. Torrey Pines Road, La Jolla, California 92037, USA.
3
Stanford Cardiovascular Institute and Department of Pediatrics, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, California 94305, USA.
4
Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
5
Imperial College London, Faculty of Medicine, Imperial Centre for Translational and Experimental Medicine, Du Cane Road, London W12 0NN, UK.
6
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, and Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
7
Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, 1417613151 Tehran, Iran.
8
Academic Medical Center. Dept Anatomy, Embryology and Physiology. Meibergdreef 15. 1105AZ Amsterdam, The Netherlands.
9
CAS Center for Excellence in Brain Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.

Abstract

The elucidation of factors that activate the regeneration of the adult mammalian heart is of major scientific and therapeutic importance. Here we found that epicardial cells contain a potent cardiogenic activity identified as follistatin-like 1 (Fstl1). Epicardial Fstl1 declines following myocardial infarction and is replaced by myocardial expression. Myocardial Fstl1 does not promote regeneration, either basally or upon transgenic overexpression. Application of the human Fstl1 protein (FSTL1) via an epicardial patch stimulates cell cycle entry and division of pre-existing cardiomyocytes, improving cardiac function and survival in mouse and swine models of myocardial infarction. The data suggest that the loss of epicardial FSTL1 is a maladaptive response to injury, and that its restoration would be an effective way to reverse myocardial death and remodelling following myocardial infarction in humans.

PMID:
26375005
PMCID:
PMC4762253
DOI:
10.1038/nature15372
[Indexed for MEDLINE]
Free PMC Article

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