PMID- 26375005
OWN - NLM
STAT- MEDLINE
DCOM- 20151019
LR  - 20240324
IS  - 1476-4687 (Electronic)
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 525
IP  - 7570
DP  - 2015 Sep 24
TI  - Epicardial FSTL1 reconstitution regenerates the adult mammalian heart.
PG  - 479-85
LID - 10.1038/nature15372 [doi]
AB  - 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.
FAU - Wei, Ke
AU  - Wei K
AD  - Department of Bioengineering, University of California, San Diego, La Jolla, 
      California 92037, USA.
AD  - Sanford-Burnham-Prebys Medical Discovery Institute, 10901 N. Torrey Pines Road, 
      La Jolla, California 92037, USA.
FAU - Serpooshan, Vahid
AU  - Serpooshan V
AD  - Stanford Cardiovascular Institute and Department of Pediatrics, Stanford 
      University School of Medicine, 300 Pasteur Drive, Stanford, California 94305, 
      USA.
FAU - Hurtado, Cecilia
AU  - Hurtado C
AD  - Department of Bioengineering, University of California, San Diego, La Jolla, 
      California 92037, USA.
AD  - Sanford-Burnham-Prebys Medical Discovery Institute, 10901 N. Torrey Pines Road, 
      La Jolla, California 92037, USA.
FAU - Diez-Cunado, Marta
AU  - Diez-Cunado M
AD  - Department of Bioengineering, University of California, San Diego, La Jolla, 
      California 92037, USA.
AD  - Sanford-Burnham-Prebys Medical Discovery Institute, 10901 N. Torrey Pines Road, 
      La Jolla, California 92037, USA.
AD  - Stanford Cardiovascular Institute and Department of Pediatrics, Stanford 
      University School of Medicine, 300 Pasteur Drive, Stanford, California 94305, 
      USA.
FAU - Zhao, Mingming
AU  - Zhao M
AD  - Stanford Cardiovascular Institute and Department of Pediatrics, Stanford 
      University School of Medicine, 300 Pasteur Drive, Stanford, California 94305, 
      USA.
FAU - Maruyama, Sonomi
AU  - Maruyama S
AD  - Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, 
      Massachusetts 02118, USA.
FAU - Zhu, Wenhong
AU  - Zhu W
AD  - Department of Bioengineering, University of California, San Diego, La Jolla, 
      California 92037, USA.
AD  - Sanford-Burnham-Prebys Medical Discovery Institute, 10901 N. Torrey Pines Road, 
      La Jolla, California 92037, USA.
FAU - Fajardo, Giovanni
AU  - Fajardo G
AD  - Stanford Cardiovascular Institute and Department of Pediatrics, Stanford 
      University School of Medicine, 300 Pasteur Drive, Stanford, California 94305, 
      USA.
FAU - Noseda, Michela
AU  - Noseda M
AD  - Imperial College London, Faculty of Medicine, Imperial Centre for Translational 
      and Experimental Medicine, Du Cane Road, London W12 0NN, UK.
FAU - Nakamura, Kazuto
AU  - Nakamura K
AD  - Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, 
      Massachusetts 02118, USA.
FAU - Tian, Xueying
AU  - Tian X
AD  - 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.
FAU - Liu, Qiaozhen
AU  - Liu Q
AD  - 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.
FAU - Wang, Andrew
AU  - Wang A
AD  - Stanford Cardiovascular Institute and Department of Pediatrics, Stanford 
      University School of Medicine, 300 Pasteur Drive, Stanford, California 94305, 
      USA.
FAU - Matsuura, Yuka
AU  - Matsuura Y
AD  - Stanford Cardiovascular Institute and Department of Pediatrics, Stanford 
      University School of Medicine, 300 Pasteur Drive, Stanford, California 94305, 
      USA.
FAU - Bushway, Paul
AU  - Bushway P
AD  - Department of Bioengineering, University of California, San Diego, La Jolla, 
      California 92037, USA.
AD  - Sanford-Burnham-Prebys Medical Discovery Institute, 10901 N. Torrey Pines Road, 
      La Jolla, California 92037, USA.
FAU - Cai, Wenqing
AU  - Cai W
AD  - Department of Bioengineering, University of California, San Diego, La Jolla, 
      California 92037, USA.
AD  - Sanford-Burnham-Prebys Medical Discovery Institute, 10901 N. Torrey Pines Road, 
      La Jolla, California 92037, USA.
FAU - Savchenko, Alex
AU  - Savchenko A
AD  - Department of Bioengineering, University of California, San Diego, La Jolla, 
      California 92037, USA.
AD  - Sanford-Burnham-Prebys Medical Discovery Institute, 10901 N. Torrey Pines Road, 
      La Jolla, California 92037, USA.
FAU - Mahmoudi, Morteza
AU  - Mahmoudi M
AD  - Stanford Cardiovascular Institute and Department of Pediatrics, Stanford 
      University School of Medicine, 300 Pasteur Drive, Stanford, California 94305, 
      USA.
AD  - Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical 
      Sciences, 1417613151 Tehran, Iran.
FAU - Schneider, Michael D
AU  - Schneider MD
AD  - Imperial College London, Faculty of Medicine, Imperial Centre for Translational 
      and Experimental Medicine, Du Cane Road, London W12 0NN, UK.
FAU - van den Hoff, Maurice J B
AU  - van den Hoff MJ
AD  - Academic Medical Center. Dept Anatomy, Embryology and Physiology. Meibergdreef 
      15. 1105AZ Amsterdam, The Netherlands.
FAU - Butte, Manish J
AU  - Butte MJ
AD  - Stanford Cardiovascular Institute and Department of Pediatrics, Stanford 
      University School of Medicine, 300 Pasteur Drive, Stanford, California 94305, 
      USA.
FAU - Yang, Phillip C
AU  - Yang PC
AD  - Stanford Cardiovascular Institute and Department of Pediatrics, Stanford 
      University School of Medicine, 300 Pasteur Drive, Stanford, California 94305, 
      USA.
FAU - Walsh, Kenneth
AU  - Walsh K
AD  - Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, 
      Massachusetts 02118, USA.
FAU - Zhou, Bin
AU  - Zhou B
AD  - 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.
AD  - CAS Center for Excellence in Brain Science, Shanghai Institutes for Biological 
      Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
FAU - Bernstein, Daniel
AU  - Bernstein D
AD  - Stanford Cardiovascular Institute and Department of Pediatrics, Stanford 
      University School of Medicine, 300 Pasteur Drive, Stanford, California 94305, 
      USA.
FAU - Mercola, Mark
AU  - Mercola M
AD  - Department of Bioengineering, University of California, San Diego, La Jolla, 
      California 92037, USA.
AD  - Sanford-Burnham-Prebys Medical Discovery Institute, 10901 N. Torrey Pines Road, 
      La Jolla, California 92037, USA.
FAU - Ruiz-Lozano, Pilar
AU  - Ruiz-Lozano P
AD  - Stanford Cardiovascular Institute and Department of Pediatrics, Stanford 
      University School of Medicine, 300 Pasteur Drive, Stanford, California 94305, 
      USA.
LA  - eng
GR  - R01 HL116591/HL/NHLBI NIH HHS/United States
GR  - RG/15/1/31165/BHF_/British Heart Foundation/United Kingdom
GR  - R01 HL113601/HL/NHLBI NIH HHS/United States
GR  - K08 AI079268/AI/NIAID NIH HHS/United States
GR  - R01 HL065484/HL/NHLBI NIH HHS/United States
GR  - R01 HL108176/HL/NHLBI NIH HHS/United States
GR  - HL116591/HL/NHLBI NIH HHS/United States
GR  - P01 HL098053/HL/NHLBI NIH HHS/United States
GR  - P30 AR061303/AR/NIAMS NIH HHS/United States
GR  - R01 HL086879/HL/NHLBI NIH HHS/United States
GR  - R56 HL065484/HL/NHLBI NIH HHS/United States
GR  - 5UM1 HL113456/HL/NHLBI NIH HHS/United States
GR  - P30 CA030199/CA/NCI NIH HHS/United States
GR  - RG/08/007/25296/BHF_/British Heart Foundation/United Kingdom
GR  - HL065484/HL/NHLBI NIH HHS/United States
GR  - UM1 HL113456/HL/NHLBI NIH HHS/United States
GR  - HL113601/HL/NHLBI NIH HHS/United States
GR  - R01 GM110482/GM/NIGMS NIH HHS/United States
GR  - HL108176/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20150916
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Follistatin-Related Proteins)
RN  - 0 (Fstl1 protein, mouse)
RN  - 158709-61-6 (FSTL1 protein, human)
SB  - IM
CIN - Nature. 2015 Sep 24;525(7570):461-2. PMID: 26375007
CIN - Nat Rev Drug Discov. 2015 Nov;14(11):747. PMID: 26471365
CIN - Trends Mol Med. 2015 Dec;21(12):731-3. PMID: 26596868
MH  - Animals
MH  - Cell Cycle/drug effects
MH  - Cell Proliferation/drug effects
MH  - Culture Media, Conditioned/pharmacology
MH  - Female
MH  - Follistatin-Related Proteins/genetics/*metabolism
MH  - Humans
MH  - Male
MH  - Mice
MH  - Myoblasts, Cardiac/cytology/drug effects
MH  - Myocardial Infarction/genetics/metabolism/pathology/physiopathology
MH  - Myocardium/*metabolism
MH  - Myocytes, Cardiac/cytology/drug effects/metabolism
MH  - Pericardium/cytology/drug effects/*growth & development/*metabolism
MH  - Rats
MH  - *Regeneration/drug effects
MH  - Signal Transduction
MH  - Swine
MH  - Transgenes/genetics
PMC - PMC4762253
MID - NIHMS745341
COIS- The authors declare no competing financial interests.
EDAT- 2015/09/17 06:00
MHDA- 2015/10/20 06:00
PMCR- 2016/02/22
CRDT- 2015/09/17 06:00
PHST- 2013/12/18 00:00 [received]
PHST- 2015/08/11 00:00 [accepted]
PHST- 2015/09/17 06:00 [entrez]
PHST- 2015/09/17 06:00 [pubmed]
PHST- 2015/10/20 06:00 [medline]
PHST- 2016/02/22 00:00 [pmc-release]
AID - nature15372 [pii]
AID - 10.1038/nature15372 [doi]
PST - ppublish
SO  - Nature. 2015 Sep 24;525(7570):479-85. doi: 10.1038/nature15372. Epub 2015 Sep 16.