PMID- 23640575
OWN - NLM
STAT- MEDLINE
DCOM- 20131105
LR  - 20211021
IS  - 1573-7209 (Electronic)
IS  - 0969-6970 (Print)
IS  - 0969-6970 (Linking)
VI  - 16
IP  - 3
DP  - 2013 Jul
TI  - Inhibition of apelin expression switches endothelial cells from proliferative to 
      mature state in pathological retinal angiogenesis.
PG  - 723-34
LID - 10.1007/s10456-013-9349-6 [doi]
AB  - The recruitment of mural cells such as pericytes to patent vessels with an 
      endothelial lumen is a key factor for the maturation of blood vessels and the 
      prevention of hemorrhage in pathological angiogenesis. To date, our understanding 
      of the specific trigger underlying the transition from cell growth to the 
      maturation phase remains incomplete. Since rapid endothelial cell growth causes 
      pericyte loss, we hypothesized that suppression of endothelial growth factors 
      would both promote pericyte recruitment, in addition to inhibiting pathological 
      angiogenesis. Here, we demonstrate that targeted knockdown of apelin in 
      endothelial cells using siRNA induced the expression of monocyte chemoattractant 
      protein-1 (MCP-1) through activation of Smad3, via suppression of the PI3K/Akt 
      pathway. The conditioned medium of endothelial cells treated with apelin siRNA 
      enhanced the migration of vascular smooth muscle cells, through MCP-1 and its 
      receptor pathway. Moreover, in vivo delivery of siRNA targeting apelin, which 
      causes exuberant endothelial cell proliferation and pathological angiogenesis 
      through its receptor APJ, led to increased pericyte coverage and suppressed 
      pathological angiogenesis in an oxygen-induced retinopathy model. These data 
      demonstrate that apelin is not only a potent endothelial growth factor, but also 
      restricts pericyte recruitment, establishing a new connection between endothelial 
      cell proliferation signaling and a trigger of mural recruitment.
FAU - Kasai, Atsushi
AU  - Kasai A
AD  - Interdisciplinary Program for Biomedical Sciences, Institute for Academic 
      Initiatives, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan. 
      kasai@phs.osaka-u.ac.jp
FAU - Ishimaru, Yuki
AU  - Ishimaru Y
FAU - Higashino, Kosuke
AU  - Higashino K
FAU - Kobayashi, Kohei
AU  - Kobayashi K
FAU - Yamamuro, Akiko
AU  - Yamamuro A
FAU - Yoshioka, Yasuhiro
AU  - Yoshioka Y
FAU - Maeda, Sadaaki
AU  - Maeda S
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130503
PL  - Germany
TA  - Angiogenesis
JT  - Angiogenesis
JID - 9814575
RN  - 0 (Adipokines)
RN  - 0 (Apelin)
RN  - 0 (Apelin Receptors)
RN  - 0 (Apln protein, mouse)
RN  - 0 (Aplnr protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (Smad3 Protein)
RN  - 0 (Smad3 protein, mouse)
SB  - IM
MH  - Adipokines
MH  - Analysis of Variance
MH  - Animals
MH  - Apelin
MH  - Apelin Receptors
MH  - Blotting, Western
MH  - Chemokine CCL2/*metabolism
MH  - Culture Media, Conditioned/pharmacology
MH  - Endothelial Cells/*cytology/metabolism
MH  - Gene Knockdown Techniques
MH  - Immunohistochemistry
MH  - Intercellular Signaling Peptides and Proteins/genetics/*metabolism
MH  - Mice
MH  - Muscle, Smooth, Vascular/metabolism
MH  - Neovascularization, Pathologic/*physiopathology
MH  - RNA, Small Interfering/pharmacology
MH  - Real-Time Polymerase Chain Reaction
MH  - Receptors, G-Protein-Coupled/metabolism
MH  - Retinal Vessels/*physiopathology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Smad3 Protein/metabolism
MH  - Tumor Cells, Cultured
PMC - PMC3682100
EDAT- 2013/05/04 06:00
MHDA- 2013/11/06 06:00
PMCR- 2013/05/03
CRDT- 2013/05/04 06:00
PHST- 2012/12/13 00:00 [received]
PHST- 2013/04/24 00:00 [accepted]
PHST- 2013/05/04 06:00 [entrez]
PHST- 2013/05/04 06:00 [pubmed]
PHST- 2013/11/06 06:00 [medline]
PHST- 2013/05/03 00:00 [pmc-release]
AID - 9349 [pii]
AID - 10.1007/s10456-013-9349-6 [doi]
PST - ppublish
SO  - Angiogenesis. 2013 Jul;16(3):723-34. doi: 10.1007/s10456-013-9349-6. Epub 2013 
      May 3.