PMID- 28434000
OWN - NLM
STAT- MEDLINE
DCOM- 20180813
LR  - 20181202
IS  - 1421-9751 (Electronic)
IS  - 0008-6312 (Linking)
VI  - 137
IP  - 3
DP  - 2017
TI  - Apolipoprotein A1 Inhibits the TGF-beta1-Induced Endothelial-to-Mesenchymal 
      Transition of Human Coronary Artery Endothelial Cells.
PG  - 179-187
LID - 10.1159/000464321 [doi]
AB  - OBJECTIVE: Transforming growth factor beta1 (TGF-beta1) is the major cytokine for 
      stimulating endothelial cells (ECs) to transdifferentiate to mesenchymal cells 
      (MCs) in the process known as endothelial-to-mesenchymal transition (EndMT). 
      Recently, TGF-beta1-induced EndMT has been implicated in the pathogenesis of 
      atherosclerosis (AS). It has been identified that apolipoprotein A1 (ApoA-I) 
      obstructs TGF-beta1-induced endothelial dysfunction, providing a protective effect 
      for ECs and also anti-AS activity. However, the exact role of ApoA-I in 
      TGF-beta1-induced EndMT is not clear. In this study, we aimed to investigate whether 
      ApoA-I can modulate TGF-beta1-induced EndMT in human coronary artery ECs (HCAECs). 
      METHODS AND RESULTS: The HCAECs were treated with TGF-beta1 with or without ApoA-I. 
      Morphological changes in HCAECs and the expression of EndMT-related markers were 
      evaluated. HCAECs treated with TGF-beta1 were found to transform to MC morphology, 
      with inconspicuous expression of EC markers such as vascular endothelial cadherin 
      and CD31, and conspicuous expression of fibroblast-specific protein 1 (FSP-1) and 
      alpha-smooth muscle actin. The treatment of HCAECs with ApoA-I inhibited the 
      TGF-beta1-induced EndMT, and elevated expression of EC markers was observed but 
      reduced expression of MC markers. Moreover, ApoA-I impeded the expression level 
      of Slug and Snail, crucial transcriptional factors of EndMT, and it inhibited the 
      TGF-beta1-induced phosphorylation of Smad2 and Smad3 which affected the EC 
      morphology. In addition, the knockdown of ABCA1 by RNA interference eliminated 
      the inhibition effect of ApoA-I on TGF-beta1-induced EndMT. CONCLUSIONS: Our 
      findings revealed a novel mechanism for the ApoA-I protective effect on 
      endothelium function via the inhibition of TGF-beta1-induced EndMT. This might 
      provide new insights for developing strategies for modulating AS and vascular 
      remodeling.
CI  - (c) 2017 S. Karger AG, Basel.
FAU - Feng, Juling
AU  - Feng J
AD  - Research Lab of Translational Medicine, Medical School, University of South 
      China, Hengyang, China.
FAU - Zhang, Jingjing
AU  - Zhang J
FAU - Jackson, Ampadu O
AU  - Jackson AO
FAU - Zhu, Xiao
AU  - Zhu X
FAU - Chen, Hainan
AU  - Chen H
FAU - Chen, Wen
AU  - Chen W
FAU - Gui, Qingjun
AU  - Gui Q
FAU - Yin, Kai
AU  - Yin K
LA  - eng
PT  - Journal Article
DEP - 20170422
PL  - Switzerland
TA  - Cardiology
JT  - Cardiology
JID - 1266406
RN  - 0 (Apolipoprotein A-I)
RN  - 0 (Smad2 Protein)
RN  - 0 (Smad3 Protein)
RN  - 0 (Transforming Growth Factor beta1)
SB  - IM
MH  - Apolipoprotein A-I/*pharmacology
MH  - *Cell Transdifferentiation
MH  - Cells, Cultured
MH  - Coronary Vessels/cytology
MH  - Endothelial Cells/*cytology/drug effects
MH  - Humans
MH  - Mesenchymal Stem Cells/*cytology/drug effects
MH  - Phosphorylation
MH  - Signal Transduction
MH  - Smad2 Protein/metabolism
MH  - Smad3 Protein/metabolism
MH  - Transforming Growth Factor beta1/*pharmacology
OTO - NOTNLM
OT  - Apolipoprotein A1
OT  - Atherosclerosis
OT  - Endothelial-to-mesenchymal transition
OT  - Transforming growth factor beta1
EDAT- 2017/04/24 06:00
MHDA- 2018/08/14 06:00
CRDT- 2017/04/24 06:00
PHST- 2016/12/20 00:00 [received]
PHST- 2017/02/20 00:00 [accepted]
PHST- 2017/04/24 06:00 [pubmed]
PHST- 2018/08/14 06:00 [medline]
PHST- 2017/04/24 06:00 [entrez]
AID - 000464321 [pii]
AID - 10.1159/000464321 [doi]
PST - ppublish
SO  - Cardiology. 2017;137(3):179-187. doi: 10.1159/000464321. Epub 2017 Apr 22.