PMID- 31781322
OWN - NLM
STAT- MEDLINE
DCOM- 20200420
LR  - 20200420
IS  - 1942-0994 (Electronic)
IS  - 1942-0900 (Print)
IS  - 1942-0994 (Linking)
VI  - 2019
DP  - 2019
TI  - miR-200a Attenuated Doxorubicin-Induced Cardiotoxicity through Upregulation of 
      Nrf2 in Mice.
PG  - 1512326
LID - 10.1155/2019/1512326 [doi]
LID - 1512326
AB  - Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) was closely involved in 
      doxorubicin- (DOX-) induced cardiotoxicity. MicroRNA-200a (miR-200a) could target 
      Keap1 mRNA and promote degradation of Keap1 mRNA, resulting in Nrf2 activation. 
      However, the role of miR-200a in DOX-related cardiotoxicity remained unclear. Our 
      study is aimed at investigating the effect of miR-200a on DOX-induced 
      cardiotoxicity in mice. For cardiotropic expression, male mice received an 
      injection of an adeno-associated virus 9 (AAV9) system carrying miR-200a or 
      miR-scramble. Four weeks later, mice received a single intraperitoneal injection 
      of DOX at 15 mg/kg. In our study, we found that miR-200a mRNA was the only 
      microRNA that was significantly decreased in DOX-treated mice and H9c2 cells. 
      miR-200a supplementation blocked whole-body wasting and heart atrophy caused by 
      acute DOX injection, decreased the levels of cardiac troponin I and the 
      N-terminal probrain natriuretic peptide, and improved cardiac and adult 
      cardiomyocyte contractile function. Moreover, miR-200a reduced oxidative stress 
      and cardiac apoptosis without affecting matrix metalloproteinase and inflammatory 
      factors in mice with acute DOX injection. miR-200a also attenuated DOX-induced 
      oxidative injury and cell loss in vitro. As expected, we found that miR-200a 
      activated Nrf2 and Nrf2 deficiency abolished the protection provided by miR-200a 
      supplementation in mice. miR-200a also provided cardiac benefits in a chronic 
      model of DOX-induced cardiotoxicity. In conclusion, miR-200a protected against 
      DOX-induced cardiotoxicity via activation of the Nrf2 signaling pathway. Our data 
      suggest that miR-200a may represent a new cardioprotective strategy against 
      DOX-induced cardiotoxicity.
CI  - Copyright (c) 2019 Xiaoping Hu et al.
FAU - Hu, Xiaoping
AU  - Hu X
AD  - Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan, 
      Hubei 430060, China.
FAU - Liu, Huagang
AU  - Liu H
AD  - Department of Vascular Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 
      430060, China.
FAU - Wang, Zhiwei
AU  - Wang Z
AUID- ORCID: 0000-0001-5643-9344
AD  - Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan, 
      Hubei 430060, China.
FAU - Hu, Zhipeng
AU  - Hu Z
AD  - Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan, 
      Hubei 430060, China.
FAU - Li, Luocheng
AU  - Li L
AD  - Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan, 
      Hubei 430060, China.
LA  - eng
PT  - Journal Article
DEP - 20191103
PL  - United States
TA  - Oxid Med Cell Longev
JT  - Oxidative medicine and cellular longevity
JID - 101479826
RN  - 0 (MicroRNAs)
RN  - 0 (Mirn200 microRNA, mouse)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Nfe2l2 protein, mouse)
RN  - 80168379AG (Doxorubicin)
SB  - IM
MH  - Animals
MH  - Cardiotoxicity/*metabolism/pathology
MH  - Doxorubicin/*adverse effects/pharmacology
MH  - Male
MH  - Mice
MH  - MicroRNAs/*metabolism
MH  - NF-E2-Related Factor 2/*biosynthesis
MH  - Oxidative Stress/drug effects
MH  - Up-Regulation/*drug effects
PMC - PMC6875222
COIS- The authors declare that they have no conflicts of interest.
EDAT- 2019/11/30 06:00
MHDA- 2020/04/21 06:00
PMCR- 2019/11/03
CRDT- 2019/11/30 06:00
PHST- 2019/05/12 00:00 [received]
PHST- 2019/08/07 00:00 [revised]
PHST- 2019/08/31 00:00 [accepted]
PHST- 2019/11/30 06:00 [entrez]
PHST- 2019/11/30 06:00 [pubmed]
PHST- 2020/04/21 06:00 [medline]
PHST- 2019/11/03 00:00 [pmc-release]
AID - 10.1155/2019/1512326 [doi]
PST - epublish
SO  - Oxid Med Cell Longev. 2019 Nov 3;2019:1512326. doi: 10.1155/2019/1512326. 
      eCollection 2019.