PMID- 31923740
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210110
IS  - 2162-2531 (Print)
IS  - 2162-2531 (Electronic)
IS  - 2162-2531 (Linking)
VI  - 19
DP  - 2020 Mar 6
TI  - MSTN Attenuates Cardiac Hypertrophy through Inhibition of Excessive Cardiac 
      Autophagy by Blocking AMPK /mTOR and miR-128/PPARgamma/NF-kappaB.
PG  - 507-522
LID - S2162-2531(19)30398-1 [pii]
LID - 10.1016/j.omtn.2019.12.003 [doi]
AB  - Cardiac hypertrophy, a response of the heart to increased workload, is a major 
      risk factor for heart failure. Myostatin (MSTN) is an inhibitor of myogenesis, 
      regulating the number and size of skeletal myocytes. In recent years, 
      cardiomyocyte autophagy also has been considered to be involved in controlling 
      the hypertrophic response. However, less is known about the detailed mechanism of 
      MSTN on cardiac hypertrophy via regulation of cardiomyocyte autophagy. In this 
      study, we found that the deletion of MSTN potentiated abdominal aorta coarctation 
      (AAC) and angiotensin II (Ang II)-induced pathological cardiac hypertrophy and 
      cardiac autophagy; however, AAC and Ang II-induced cardiac hypertrophic phenotype 
      and cardiac autophagy were dramatically diminished by MSTN in vivo and in vitro. 
      Mechanistically, the anti-hypertrophic and anti-autophagic effects mediated by 
      MSTN in response to pathological stimuli were associated with the direct 
      inactivation of activated protein kinase (AMPK)/mammalian target of rapamycin 
      (mTOR) and activation of the peroxisome proliferator-activated receptor gamma 
      (PPARgamma)/nuclear factor kappaB (NF-kappaB) signaling pathway. Additionally, miR-128 
      aggravated the progression of cardiac hypertrophy through suppressing its target 
      PPARgamma. Furthermore, MSTN downregulated miR-128 expression induced by AAC and Ang 
      II. Taken together, MSTN significantly blunts pathological cardiac hypertrophy 
      and dysfunction, at least in part, by inhibiting excessive cardiac autophagy via 
      blocking AMPK/mTOR and miR-128/PPARgamma/NF-kappaB signaling pathways.
CI  - Copyright (c) 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Qi, Hanping
AU  - Qi H
AD  - Department of Pharmacology, Harbin Medical University-Daqing, Daqing, 
      Heilongjiang 163319, China.
FAU - Ren, Jing
AU  - Ren J
AD  - Department of Pharmacology, Harbin Medical University-Daqing, Daqing, 
      Heilongjiang 163319, China.
FAU - Ba, Lina
AU  - Ba L
AD  - Department of Pharmacology, Harbin Medical University-Daqing, Daqing, 
      Heilongjiang 163319, China.
FAU - Song, Chao
AU  - Song C
AD  - Department of Pharmacology, Harbin Medical University-Daqing, Daqing, 
      Heilongjiang 163319, China.
FAU - Zhang, Qianhui
AU  - Zhang Q
AD  - Department of Pharmacology, Harbin Medical University-Daqing, Daqing, 
      Heilongjiang 163319, China.
FAU - Cao, Yonggang
AU  - Cao Y
AD  - Department of Pharmacology, Harbin Medical University-Daqing, Daqing, 
      Heilongjiang 163319, China.
FAU - Shi, Pilong
AU  - Shi P
AD  - Department of Pharmacology, Harbin Medical University-Daqing, Daqing, 
      Heilongjiang 163319, China.
FAU - Fu, Bowen
AU  - Fu B
AD  - Department of Pharmacology, Harbin Medical University-Daqing, Daqing, 
      Heilongjiang 163319, China.
FAU - Liu, Yongsheng
AU  - Liu Y
AD  - Department of Pharmacology, Harbin Medical University-Daqing, Daqing, 
      Heilongjiang 163319, China.
FAU - Sun, Hongli
AU  - Sun H
AD  - Department of Pharmacology, Harbin Medical University-Daqing, Daqing, 
      Heilongjiang 163319, China. Electronic address: hlsun2002@163.com.
LA  - eng
PT  - Journal Article
DEP - 20191214
PL  - United States
TA  - Mol Ther Nucleic Acids
JT  - Molecular therapy. Nucleic acids
JID - 101581621
PMC - PMC6951838
OTO - NOTNLM
OT  - AMPK
OT  - MSTN
OT  - PPARgamma
OT  - autophagy
OT  - cardiac hypertrophy
OT  - miR-128
EDAT- 2020/01/11 06:00
MHDA- 2020/01/11 06:01
PMCR- 2019/12/14
CRDT- 2020/01/11 06:00
PHST- 2019/05/09 00:00 [received]
PHST- 2019/11/17 00:00 [revised]
PHST- 2019/12/02 00:00 [accepted]
PHST- 2020/01/11 06:00 [pubmed]
PHST- 2020/01/11 06:01 [medline]
PHST- 2020/01/11 06:00 [entrez]
PHST- 2019/12/14 00:00 [pmc-release]
AID - S2162-2531(19)30398-1 [pii]
AID - 10.1016/j.omtn.2019.12.003 [doi]
PST - ppublish
SO  - Mol Ther Nucleic Acids. 2020 Mar 6;19:507-522. doi: 10.1016/j.omtn.2019.12.003. 
      Epub 2019 Dec 14.