PMID- 24039710
OWN - NLM
STAT- MEDLINE
DCOM- 20140610
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 9
DP  - 2013
TI  - Myocardial injection of apelin-overexpressing bone marrow cells improves cardiac 
      repair via upregulation of Sirt3 after myocardial infarction.
PG  - e71041
LID - 10.1371/journal.pone.0071041 [doi]
LID - e71041
AB  - Our previous study shows that treatment with apelin increases bone marrow cells 
      (BMCs) recruitment and promotes cardiac repair after myocardial infarction (MI). 
      The objective of this study was to investigate whether overexpression of apelin 
      in BMCs improved cell therapy and accelerated cardiac repair and functional 
      recovery in post-MI mice. Mouse myocardial infarction was achieved by coronary 
      artery ligation and BMCs overexpressing apelin (apelin-BMCs) or GFP (GFP-BMCs) 
      were injected into ischemic area immediately after surgery. In vitro, exposure of 
      cultured BMCs to apelin led to a gradual increase in SDF-1a and CXCR4 expression. 
      Intramyocardial delivery of apelin-BMCs in post-MI mice resulted in a significant 
      increase number of APJ(+)/c-kit(+)/Sca1(+) cells in the injected area compared to 
      GFP-BMCs treated post-MI mice. Treatment with apelin-BMCs increased expression of 
      VEGF, Ang-1 and Tie-2 in post-MI mice. Apelin-BMCs treatment also significantly 
      increased angiogenesis and attenuated cardiac fibrosis formation in post-MI mice. 
      Most importantly, treatment with apelin-BMCs significantly improved left 
      ventricular (LV) systolic function in post-MI mice. Mechanistically, Apelin-BMCs 
      treatment led to a significant increase in Sirtuin3 (Sirt3) expression and 
      reduction of reactive oxygen species (ROS) formation. Treatment of cultured BMCs 
      with apelin also increased Notch3 expression and Akt phosphorylation. Apelin 
      treatment further attenuated stress-induced apoptosis whereas knockout of Sirt3 
      abolished anti-apoptotic effect of apelin in cultured BMCs. Moreover, knockout of 
      Sirt3 significantly attenuated apelin-BMCs-induced VEGF expression and 
      angiogenesis in post-MI mice. Knockout of Sirt3 further blunted 
      apelin-BMCs-mediated improvement of cardiac repair and systolic functional 
      recovery in post-MI mice. These data suggest that apelin improves BMCs therapy on 
      cardiac repair and systolic function in post-MI mice. Upregulation of Sirt3 may 
      contribute to the protective effect of apelin-BMCs therapy.
FAU - Li, Lanfang
AU  - Li L
AD  - Department of Pharmacology and Toxicology, University of Mississippi Medical 
      Center, Jackson, Mississippi, United States of America.
FAU - Zeng, Heng
AU  - Zeng H
FAU - Hou, Xuwei
AU  - Hou X
FAU - He, Xiaochen
AU  - He X
FAU - Chen, Jian-Xiong
AU  - Chen JX
LA  - eng
GR  - R01 HL102042/HL/NHLBI NIH HHS/United States
GR  - HL102042/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130906
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Adipokines)
RN  - 0 (Angiogenic Proteins)
RN  - 0 (Apelin)
RN  - 0 (Apln protein, mouse)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Sirt3 protein, mouse)
RN  - EC 3.5.1.- (Sirtuin 3)
SB  - IM
MH  - Adipokines
MH  - Angiogenic Proteins/metabolism
MH  - Animals
MH  - Apelin
MH  - Bone Marrow Cells/metabolism
MH  - Bone Marrow Transplantation
MH  - Cardiomegaly/prevention & control
MH  - Cells, Cultured
MH  - Coronary Vessels/physiopathology
MH  - Enzyme Induction
MH  - Fibrosis
MH  - Intercellular Signaling Peptides and Proteins/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Myocardial Contraction
MH  - Myocardial Infarction/enzymology/physiopathology/*therapy
MH  - Myocardium/*enzymology/pathology
MH  - Neovascularization, Physiologic
MH  - Reactive Oxygen Species/metabolism
MH  - *Regeneration
MH  - Sirtuin 3/*metabolism
MH  - Up-Regulation
PMC - PMC3765164
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/09/17 06:00
MHDA- 2014/06/11 06:00
PMCR- 2013/09/06
CRDT- 2013/09/17 06:00
PHST- 2013/02/04 00:00 [received]
PHST- 2013/06/26 00:00 [accepted]
PHST- 2013/09/17 06:00 [entrez]
PHST- 2013/09/17 06:00 [pubmed]
PHST- 2014/06/11 06:00 [medline]
PHST- 2013/09/06 00:00 [pmc-release]
AID - PONE-D-13-05351 [pii]
AID - 10.1371/journal.pone.0071041 [doi]
PST - epublish
SO  - PLoS One. 2013 Sep 6;8(9):e71041. doi: 10.1371/journal.pone.0071041. eCollection 
      2013.