PMID- 27592408
OWN - NLM
STAT- MEDLINE
DCOM- 20170220
LR  - 20170220
IS  - 1532-2785 (Electronic)
IS  - 0143-4179 (Linking)
VI  - 60
DP  - 2016 Dec
TI  - Apelin-13 protects neurovascular unit against ischemic injuries through the 
      effects of vascular endothelial growth factor.
PG  - 67-74
LID - S0143-4179(16)30118-4 [pii]
LID - 10.1016/j.npep.2016.08.006 [doi]
AB  - Apelin-13 has protective effects on many neurological diseases, including 
      cerebral ischemia. Here, we aimed to test Apelin-13's effects on ischemic 
      neurovascular unit (NVU) injuries and investigate whether the effects were 
      dependent on vascular endothelial growth factor (VEGF). We detected the 
      expression of VEGF and its receptors (VEGFRs) induced by Apelin-13 injection at 
      1d, 3d, 7d and 14d after middle cerebral artery occlusion (MCAO). Meanwhile, we 
      examined the effects of Apelin-13 on NVU in both in vivo and in vitro experiments 
      as well as whether the effects were VEGF dependent by using VEGF antibody. We 
      also assessed the related signal transduction pathways via multiple inhibitors. 
      We demonstrated Apelin-13 highly increased VEGF and VEGFR-2 expression, not 
      VEGFR-1. Importantly, Apelin-13 led to neurological functions improvement by 
      associating with promotion of angiogenesis as well as reduction of neuronal death 
      and astrocyte activation, which was markedly blocked by VEGF antibody. In cell 
      cultures, Apelin-13 protected neurons, astrocytes and endothelial cells against 
      oxygen-glucose deprivation (OGD) injuries. Moreover, the effect of Apelin-13 to 
      up-regulate VEGF was suppressed by extracellular signal-regulated kinase (ERK) 
      inhibitor U0126 and phosphatidylinositol 3'-kinase (PI3K) inhibitor LY294002. Our 
      data suggest protective effects of Apelin-13 on ischemic NVU injuries are highly 
      associated with the increase of VEGF binding to VEGFR-2, possibly acting through 
      activation of ERK and PI3K/Akt pathways.
CI  - Copyright (c) 2016. Published by Elsevier Ltd.
FAU - Huang, Chuyi
AU  - Huang C
AD  - Department of Neurology, Shanghai Jiaotong University Affiliated Sixth People's 
      Hospital, No. 600 Yishan Road, Shanghai 200030, China.
FAU - Dai, Chuanfu
AU  - Dai C
AD  - Department of Otolaryngology, Head and Neck Surgery, Beijing Tsinghua Changgung 
      Hospital, Beijing 102218, China.
FAU - Gong, Kai
AU  - Gong K
AD  - School of Medicine, Tsinghua University, No. 30 Shuangqing Road, Haidian 
      District, Beijing 100084, China.
FAU - Zuo, Huancong
AU  - Zuo H
AD  - Department of Neurosurgery, Tsinghua University Yuquan Hospital, No. 5 
      Shijingshan Road, Shijingshan District, Beijing 100049, China. Electronic 
      address: zuohc@tsinghua.edu.cn.
FAU - Chu, Heling
AU  - Chu H
AD  - Department of Neurology, Huashan Hospital, Fudan University, No. 12 Mid. Wulumuqi 
      Road, Shanghai 200040, China. Electronic address: chuheling85@163.com.
LA  - eng
PT  - Journal Article
DEP - 20160816
PL  - Netherlands
TA  - Neuropeptides
JT  - Neuropeptides
JID - 8103156
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (apelin-13 peptide)
RN  - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2)
SB  - IM
MH  - Animals
MH  - Astrocytes/drug effects/metabolism
MH  - Brain Ischemia/drug therapy/metabolism/*prevention & control
MH  - Cell Survival/drug effects
MH  - Infarction, Middle Cerebral Artery/*metabolism
MH  - Intercellular Signaling Peptides and Proteins/pharmacology/*therapeutic use
MH  - Male
MH  - Neurons/drug effects/metabolism
MH  - Neuroprotective Agents/pharmacology/*therapeutic use
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/*drug effects
MH  - Vascular Endothelial Growth Factor A/*metabolism
MH  - Vascular Endothelial Growth Factor Receptor-2/*metabolism
OTO - NOTNLM
OT  - Apelin-13
OT  - Cerebral ischemia
OT  - Neurovascular unit
OT  - Vascular endothelial growth factor
EDAT- 2016/09/07 06:00
MHDA- 2016/09/07 06:01
CRDT- 2016/09/05 06:00
PHST- 2016/02/10 00:00 [received]
PHST- 2016/08/05 00:00 [revised]
PHST- 2016/08/14 00:00 [accepted]
PHST- 2016/09/07 06:00 [pubmed]
PHST- 2016/09/07 06:01 [medline]
PHST- 2016/09/05 06:00 [entrez]
AID - S0143-4179(16)30118-4 [pii]
AID - 10.1016/j.npep.2016.08.006 [doi]
PST - ppublish
SO  - Neuropeptides. 2016 Dec;60:67-74. doi: 10.1016/j.npep.2016.08.006. Epub 2016 Aug 
      16.