PMID- 31182988
OWN - NLM
STAT- MEDLINE
DCOM- 20191216
LR  - 20200225
IS  - 1942-0994 (Electronic)
IS  - 1942-0900 (Print)
IS  - 1942-0994 (Linking)
VI  - 2019
DP  - 2019
TI  - Exosomes Derived from TIMP2-Modified Human Umbilical Cord Mesenchymal Stem Cells 
      Enhance the Repair Effect in Rat Model with Myocardial Infarction Possibly by the 
      Akt/Sfrp2 Pathway.
PG  - 1958941
LID - 10.1155/2019/1958941 [doi]
LID - 1958941
AB  - Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs) are a 
      promising new therapeutic option for myocardial infarction (MI). The tissue 
      matrix metalloproteinase inhibitor 2, also known as TIMP2, is a member of the 
      tissue inhibitor family of metalloproteinases. Since TIMP2-mediated inhibition of 
      matrix metalloproteinases (MMPs) is a key determinant of post-MI remodeling, we 
      analyzed the therapeutic effects of exosomes derived from TIMP2-overexpressing 
      hucMSCs (huc-exo(TIMP2)) on the MI rat model. The huc-exo(TIMP2) significantly 
      improved in vivo cardiac function as measured by echocardiography and promoted 
      angiogenesis in MI injury. It also restricted extracellular matrix (ECM) 
      remodeling, as indicated by the reduced collagen deposition. In addition, 
      huc-exo(TIMP2) administration increased the in situ expression of the 
      antiapoptotic Bcl-2 and decreased that of the proapoptotic Bax and pro-caspase-9 
      in the infracted myocardium. Meanwhile, huc-exo(TIMP2) upregulated superoxide 
      dismutase (SOD) as well as glutathione (GSH) and decreased the malondialdehyde 
      (MDA) level in MI models. In vitro huc-exo(TIMP2) pretreatment could inhibit 
      H(2)O(2)-mediated H9C2-cardiomyocyte apoptosis and promote human umbilical vein 
      endothelial cell (HUVEC) proliferation, migration, and tube formation, as well as 
      decrease TGFbeta-induced MMP2, MMP9, and alpha-SMA secretion by cardiac fibroblasts 
      (CFs). Besides that, huc-exo(TIMP2) pretreatment also increased the expression of 
      Akt phosphorylation in the infarcted myocardium, which may relate to a high level 
      of secreted frizzled-related protein 2 (Sfrp2) in huc-exo(TIMP2), indicating a 
      mechanistic basis of its action. Importantly, Sfrp2 knockdown in huc-exo(TIMP2) 
      abrogated the protective effects. Taken together, huc-exo(TIMP2) improved cardiac 
      function by alleviating MI-induced oxidative stress and ECM remodeling, partly 
      via the Akt/Sfrp2 pathway.
FAU - Ni, Jing
AU  - Ni J
AD  - Department of Cardiology, Shanghai Tenth People's Hospital, Shanghai, China.
FAU - Liu, Xijun
AU  - Liu X
AD  - Department of Cardiology, Shanghai Tenth People's Hospital, Shanghai, China.
AD  - Pan-Vascular Research Institute, Heart, Lung, and Blood Center, Tongji University 
      School of Medicine, Shanghai, China.
FAU - Yin, Yiheng
AU  - Yin Y
AD  - Pan-Vascular Research Institute, Heart, Lung, and Blood Center, Tongji University 
      School of Medicine, Shanghai, China.
FAU - Zhang, Peiyu
AU  - Zhang P
AD  - Department of Cardiology, Shanghai Tenth People's Hospital, Shanghai, China.
FAU - Xu, Ya-Wei
AU  - Xu YW
AD  - Department of Cardiology, Shanghai Tenth People's Hospital, Shanghai, China.
AD  - Pan-Vascular Research Institute, Heart, Lung, and Blood Center, Tongji University 
      School of Medicine, Shanghai, China.
FAU - Liu, Zheng
AU  - Liu Z
AUID- ORCID: 0000-0001-6952-3406
AD  - Department of Cardiology, Shanghai Tenth People's Hospital, Shanghai, China.
AD  - Pan-Vascular Research Institute, Heart, Lung, and Blood Center, Tongji University 
      School of Medicine, Shanghai, China.
LA  - eng
PT  - Journal Article
DEP - 20190428
PL  - United States
TA  - Oxid Med Cell Longev
JT  - Oxidative medicine and cellular longevity
JID - 101479826
RN  - 0 (Membrane Proteins)
RN  - 0 (Sfrp2 protein, rat)
RN  - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2)
RN  - 4Y8F71G49Q (Malondialdehyde)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Apoptosis/physiology
MH  - Cell Proliferation/physiology
MH  - Exosomes/*metabolism
MH  - Human Umbilical Vein Endothelial Cells
MH  - Humans
MH  - Malondialdehyde/metabolism
MH  - Membrane Proteins/*metabolism
MH  - Mesenchymal Stem Cells/*cytology/*metabolism
MH  - Myocardial Infarction/*therapy
MH  - Oxidative Stress/physiology
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Rats
MH  - Tissue Inhibitor of Metalloproteinase-2/*metabolism
MH  - Umbilical Cord/*cytology
PMC - PMC6512021
EDAT- 2019/06/12 06:00
MHDA- 2019/12/18 06:00
PMCR- 2019/04/28
CRDT- 2019/06/12 06:00
PHST- 2019/01/08 00:00 [received]
PHST- 2019/03/11 00:00 [accepted]
PHST- 2019/06/12 06:00 [entrez]
PHST- 2019/06/12 06:00 [pubmed]
PHST- 2019/12/18 06:00 [medline]
PHST- 2019/04/28 00:00 [pmc-release]
AID - 10.1155/2019/1958941 [doi]
PST - epublish
SO  - Oxid Med Cell Longev. 2019 Apr 28;2019:1958941. doi: 10.1155/2019/1958941. 
      eCollection 2019.