PMID- 31210321
OWN - NLM
STAT- MEDLINE
DCOM- 20200925
LR  - 20200925
IS  - 2284-0729 (Electronic)
IS  - 1128-3602 (Linking)
VI  - 23
IP  - 11
DP  - 2019 Jun
TI  - HSP20-mediated cardiomyocyte exosomes improve cardiac function in mice with 
      myocardial infarction by activating Akt signaling pathway.
PG  - 4873-4881
LID - 18075 [pii]
LID - 10.26355/eurrev_201906_18075 [doi]
AB  - OBJECTIVE: To explore the role of heat shock protein 20 (HSP20)-mediated 
      cardiomyocyte exosomes in the cardiac function in mice with myocardial infarction 
      via the activation of the protein kinase B (Akt) signaling pathway. MATERIALS AND 
      METHODS: A total of 30 mice were enrolled to establish the model of myocardial 
      infarction. Next, these mice were divided into three groups, namely Blank group 
      (healthy mice), Model group (mouse models of myocardial infarction), and HSP20 
      group (mouse models of myocardial infarction transfected with lentivirus to 
      overexpress HSP20). After that, terminal deoxynucleotidyl transferase-mediated 
      dUTP nick end labeling (TUNEL) staining assay was performed to detect myocardial 
      apoptosis. Reactive oxygen species (ROS) accumulation in myocardial tissues was 
      determined via dihydroethidium (DHE) staining assay. Western blotting was 
      employed to analyze the expression level of Akt. The expression levels of 
      inflammatory factors tumor necrosis factor-alpha (TNF-alpha) and interleukin 1 beta 
      (IL-1beta) in HSP20-mediated cardiomyocyte exosomes were measured through 
      quantitative real time polymerase chain reaction (qRT-PCR). RESULTS: Compared 
      with that in Blank group, the number of cardiomyocyte exosomes was increased in 
      Model group and HSP20 group under anoxic conditions (p<0.05). The results of 
      quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) proved that the HSP20 
      messenger ribonucleic acid (mRNA) expression in mediated cardiomyocyte exosomes 
      was significantly lower in Model group than that in Blank group (p<0.05), while 
      in HSP20 group, it was overtly higher than that in Model group but clearly 
      lowered compared with that in Blank group (p<0.05). The protein expression of Akt 
      in cardiomyocyte exosomes was evidently decreased in Model group compared with 
      that in Blank group (p<0.05), while it was notably increased in HSP20 group 
      compared with that in Model group (p<0.05). In comparison with Blank group, Model 
      group had significantly elevated mRNA expression levels of TNF-alpha and IL-1beta. The 
      mRNA expression levels of TNF-alpha and IL-1beta in HSP20 group were remarkably lower 
      than those in Model group (p<0.05). The results of TUNEL assay revealed that the 
      overexpression of HSP20 affected myocardial apoptosis. The myocardial apoptosis 
      index in Model group [(38.42+/-2.52) %] was higher than that in Blank group 
      [(9.74+/-1.21) %], HSP20 group had a significantly decreased myocardial apoptosis 
      index [(22.36+/-2.13) %] in comparison with Model group (p<0.05). In accordance 
      with DHE staining comparison, the accumulation of ROS in myocardial tissues in 
      Model group was significantly higher than that in Blank group (p<0.05) and HSP20 
      group (p<0.05). CONCLUSIONS: We demonstrated that HSP20-mediated cardiomyocyte 
      exosomes activate the AKT signaling pathway, repress TNF-alpha and IL-1beta factors, and 
      alleviate myocardial infarction.
FAU - Yu, D-W
AU  - Yu DW
AD  - Department of Cardiovascular Medicine, Yantaishan Hospital, Yantai, China. 
      374339605@qq.com.
FAU - Ge, P-P
AU  - Ge PP
FAU - Liu, A-L
AU  - Liu AL
FAU - Yu, X-Y
AU  - Yu XY
FAU - Liu, T-T
AU  - Liu TT
LA  - eng
PT  - Journal Article
PL  - Italy
TA  - Eur Rev Med Pharmacol Sci
JT  - European review for medical and pharmacological sciences
JID - 9717360
RN  - 0 (HSP20 Heat-Shock Proteins)
RN  - 0 (IL1B protein, mouse)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Tnf protein, mouse)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.1 (Akt1 protein, mouse)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Exosomes/*metabolism/ultrastructure
MH  - HSP20 Heat-Shock Proteins/genetics/*metabolism
MH  - Humans
MH  - Interleukin-1beta/metabolism
MH  - Male
MH  - Mice
MH  - Microscopy, Electron, Transmission
MH  - Myocardial Infarction/*pathology
MH  - Myocardium/cytology/pathology
MH  - Myocytes, Cardiac/metabolism/*ultrastructure
MH  - Primary Cell Culture
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 2019/06/19 06:00
MHDA- 2020/09/26 06:00
CRDT- 2019/06/19 06:00
PHST- 2019/06/19 06:00 [entrez]
PHST- 2019/06/19 06:00 [pubmed]
PHST- 2020/09/26 06:00 [medline]
AID - 18075 [pii]
AID - 10.26355/eurrev_201906_18075 [doi]
PST - ppublish
SO  - Eur Rev Med Pharmacol Sci. 2019 Jun;23(11):4873-4881. doi: 
      10.26355/eurrev_201906_18075.