Publication Date:
2015-09-17
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4762253/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4762253/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wei, Ke -- Serpooshan, Vahid -- Hurtado, Cecilia -- Diez-Cunado, Marta -- Zhao, Mingming -- Maruyama, Sonomi -- Zhu, Wenhong -- Fajardo, Giovanni -- Noseda, Michela -- Nakamura, Kazuto -- Tian, Xueying -- Liu, Qiaozhen -- Wang, Andrew -- Matsuura, Yuka -- Bushway, Paul -- Cai, Wenqing -- Savchenko, Alex -- Mahmoudi, Morteza -- Schneider, Michael D -- van den Hoff, Maurice J B -- Butte, Manish J -- Yang, Phillip C -- Walsh, Kenneth -- Zhou, Bin -- Bernstein, Daniel -- Mercola, Mark -- Ruiz-Lozano, Pilar -- 5UM1 HL113456/HL/NHLBI NIH HHS/ -- HL065484/HL/NHLBI NIH HHS/ -- HL108176/HL/NHLBI NIH HHS/ -- HL113601/HL/NHLBI NIH HHS/ -- HL116591/HL/NHLBI NIH HHS/ -- K08 AI079268/AI/NIAID NIH HHS/ -- P01 HL098053/HL/NHLBI NIH HHS/ -- P30 AR061303/AR/NIAMS NIH HHS/ -- P30 CA030199/CA/NCI NIH HHS/ -- R01 HL086879/HL/NHLBI NIH HHS/ -- R01 HL113601/HL/NHLBI NIH HHS/ -- UM1 HL113456/HL/NHLBI NIH HHS/ -- England -- Nature. 2015 Sep 24;525(7570):479-85. doi: 10.1038/nature15372. Epub 2015 Sep 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioengineering, University of California, San Diego, La Jolla, California 92037, USA. ; Sanford-Burnham-Prebys Medical Discovery Institute, 10901 N. Torrey Pines Road, La Jolla, California 92037, USA. ; Stanford Cardiovascular Institute and Department of Pediatrics, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, California 94305, USA. ; Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts 02118, USA. ; Imperial College London, Faculty of Medicine, Imperial Centre for Translational and Experimental Medicine, Du Cane Road, London W12 0NN, UK. ; 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. ; Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, 1417613151 Tehran, Iran. ; Academic Medical Center. Dept Anatomy, Embryology and Physiology. Meibergdreef 15. 1105AZ Amsterdam, The Netherlands. ; CAS Center for Excellence in Brain Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26375005" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Cell Cycle/drug effects
;
Cell Proliferation/drug effects
;
Culture Media, Conditioned/pharmacology
;
Female
;
Follistatin-Related Proteins/genetics/*metabolism
;
Humans
;
Male
;
Mice
;
Myoblasts, Cardiac/cytology/drug effects
;
Myocardial Infarction/genetics/metabolism/pathology/physiopathology
;
Myocardium/*metabolism
;
Myocytes, Cardiac/cytology/drug effects/metabolism
;
Pericardium/cytology/drug effects/*growth & development/*metabolism
;
Rats
;
*Regeneration/drug effects
;
Signal Transduction
;
Swine
;
Transgenes/genetics
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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