PMID- 28271613
OWN - NLM
STAT- MEDLINE
DCOM- 20180430
LR  - 20211204
IS  - 1582-4934 (Electronic)
IS  - 1582-1838 (Print)
IS  - 1582-1838 (Linking)
VI  - 21
IP  - 9
DP  - 2017 Sep
TI  - Qiliqiangxin protects against anoxic injury in cardiac microvascular endothelial 
      cells via NRG-1/ErbB-PI3K/Akt/mTOR pathway.
PG  - 1905-1914
LID - 10.1111/jcmm.13111 [doi]
AB  - Cardiac microvascular endothelial cells (CMECs) are important angiogenic 
      components and are injured rapidly after cardiac ischaemia and anoxia. 
      Cardioprotective effects of Qiliqiangxin (QL), a traditional Chinese medicine, 
      have been displayed recently. This study aims to investigate whether QL could 
      protect CMECs against anoxic injury and to explore related signalling mechanisms. 
      CMECs were successfully cultured from Sprague-Dawley rats and exposed to anoxia 
      for 12 hrs in the absence and presence of QL. Cell migration assay and 
      capillary-like tube formation assay on Matrigel were performed, and cell 
      apoptosis was determined by TUNEL assay and caspase-3 activity. Neuregulin-1 
      (NRG-1) siRNA and LY294002 were administrated to block NRG-1/ErbB and PI3K/Akt 
      signalling, respectively. As a result, anoxia inhibited cell migration, 
      capillary-like tube formation and angiogenesis, and increased cell apoptosis. QL 
      significantly reversed these anoxia-induced injuries and up-regulated expressions 
      of NRG-1, phospho-ErbB2, phospho-ErbB4, phospho-Akt, phospho-mammalian target of 
      rapamycin (mTOR), hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial 
      growth factor (VEGF) in CMECs, while NRG-1 knockdown abolished the protective 
      effects of QL with suppressed NRG-1, phospho-ErbB2, phospho-ErbB4, phospho-Akt, 
      phospho-mTOR, HIF-1alpha and VEGF expressions. Similarly, LY294002 interrupted the 
      beneficial effects of QL with down-regulated phospho-Akt, phospho-mTOR, HIF-1alpha 
      and VEGF expressions. However, it had no impact on NRG-1/ErbB signalling. Our 
      data indicated that QL could attenuate anoxia-induced injuries in CMECs via 
      NRG-1/ErbB signalling which was most probably dependent on PI3K/Akt/mTOR pathway.
CI  - (c) 2017 The Authors. Journal of Cellular and Molecular Medicine published by John 
      Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
FAU - Wang, Jingfeng
AU  - Wang J
AD  - Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, 
      Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Zhou, Jingmin
AU  - Zhou J
AD  - Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, 
      Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Wang, Yanyan
AU  - Wang Y
AD  - Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, 
      Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Yang, Chunjie
AU  - Yang C
AD  - Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, 
      Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Fu, Mingqiang
AU  - Fu M
AD  - Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, 
      Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Zhang, Jingjing
AU  - Zhang J
AD  - Department of Cardiology, Shandong University, Jinan, Shandong, China.
FAU - Han, Xueting
AU  - Han X
AD  - Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, 
      Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Li, Zhiming
AU  - Li Z
AD  - Department of Cardiology, People's Hospital of Nanbu County, Nanchong, Sichuan, 
      China.
FAU - Hu, Kai
AU  - Hu K
AD  - Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, 
      Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Ge, Junbo
AU  - Ge J
AD  - Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, 
      Zhongshan Hospital, Fudan University, Shanghai, China.
LA  - eng
PT  - Journal Article
DEP - 20170308
PL  - England
TA  - J Cell Mol Med
JT  - Journal of cellular and molecular medicine
JID - 101083777
RN  - 0 (Cardiotonic Agents)
RN  - 0 (Chromones)
RN  - 0 (Drugs, Chinese Herbal)
RN  - 0 (Morpholines)
RN  - 0 (Neuregulin-1)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (qiliqiangxin)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Animals
MH  - Cardiotonic Agents/*pharmacology
MH  - Caspase 3/metabolism
MH  - Cell Hypoxia/drug effects
MH  - Cell Movement/drug effects
MH  - Cell Separation
MH  - Cells, Cultured
MH  - Chromones/pharmacology
MH  - Drugs, Chinese Herbal/*pharmacology
MH  - Endothelial Cells/drug effects/*metabolism
MH  - Gene Knockdown Techniques
MH  - Male
MH  - Microvessels/*pathology
MH  - Morpholines/pharmacology
MH  - Myocardium/*pathology
MH  - Neovascularization, Physiologic/drug effects
MH  - Neuregulin-1/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - RNA, Small Interfering/metabolism
MH  - Rats, Sprague-Dawley
MH  - Receptor, ErbB-2/metabolism
MH  - Signal Transduction/*drug effects
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Up-Regulation/drug effects
PMC - PMC5571527
OTO - NOTNLM
OT  - Qiliqiangxin
OT  - angiogenesis
OT  - anoxia
OT  - apoptosis
OT  - cardiac microvascular endothelial cell
OT  - neuregulin
EDAT- 2017/03/09 06:00
MHDA- 2018/05/01 06:00
PMCR- 2017/09/01
CRDT- 2017/03/09 06:00
PHST- 2016/08/10 00:00 [received]
PHST- 2016/12/25 00:00 [accepted]
PHST- 2017/03/09 06:00 [pubmed]
PHST- 2018/05/01 06:00 [medline]
PHST- 2017/03/09 06:00 [entrez]
PHST- 2017/09/01 00:00 [pmc-release]
AID - JCMM13111 [pii]
AID - 10.1111/jcmm.13111 [doi]
PST - ppublish
SO  - J Cell Mol Med. 2017 Sep;21(9):1905-1914. doi: 10.1111/jcmm.13111. Epub 2017 Mar 
      8.