PMID- 24563071
OWN - NLM
STAT- MEDLINE
DCOM- 20150204
LR  - 20211203
IS  - 1573-7209 (Electronic)
IS  - 0969-6970 (Print)
IS  - 0969-6970 (Linking)
VI  - 17
IP  - 3
DP  - 2014 Jul
TI  - Angiopoietin-like protein 2 regulates endothelial colony forming cell 
      vasculogenesis.
PG  - 675-83
LID - 10.1007/s10456-014-9423-8 [doi]
AB  - Angiopoietin-like 2 (ANGPTL2) has been reported to induce sprouting angiogenesis; 
      however, its role in vasculogenesis, the de novo lumenization of endothelial 
      cells (EC), remains unexplored. We sought to investigate the potential role of 
      ANGPTL2 in regulating human cord blood derived endothelial colony forming cell 
      (ECFC) vasculogenesis through siRNA mediated inhibition of ANGPTL2 gene 
      expression. We found that ECFCs in which ANGPTL2 was diminished displayed a 
      threefold decrease in in vitro lumenal area whereas addition of exogenous ANGPTL2 
      protein domains to ECFCs lead to increased lumen formation within a 3 dimensional 
      (3D) collagen assay of vasculogenesis. ECFC migration was attenuated by 36 % via 
      ANGPTL2 knockdown (KD) although proliferation and apoptosis were not affected. We 
      subsequently found that c-Jun NH2-terminal kinase (JNK), but not ERK1/2, 
      phosphorylation was decreased upon ANGPTL2 KD, and expression of membrane type 1 
      matrix metalloproteinase (MT1-MMP), known to be regulated by JNK and a critical 
      regulator of EC migration and 3D lumen formation, was decreased in lumenized 
      structures in vitro derived from ANGPTL2 silenced ECFCs. Treatment of ECFCs in 3D 
      collagen matrices with either a JNK inhibitor or exogenous rhTIMP-3 (an inhibitor 
      of MT1-MMP activity) resulted in a similar phenotype of decreased vascular lumen 
      formation as observed with ANGPTL2 KD, whereas stimulation of JNK activity 
      increased vasculogenesis. Based on gene silencing, pharmacologic, cellular, and 
      biochemical approaches, we conclude that ANGPTL2 positively regulates ECFC 
      vascular lumen formation likely through its effects on migration and in part by 
      activating JNK and increasing MT1-MMP expression.
FAU - Richardson, Matthew R
AU  - Richardson MR
AD  - Wells Center for Pediatric Research, Indiana University School of Medicine, 1044 
      W. Walnut Street, R4-W125, Indianapolis, IN, 46202, USA.
FAU - Robbins, Emilie P
AU  - Robbins EP
FAU - Vemula, Sasidhar
AU  - Vemula S
FAU - Critser, Paul J
AU  - Critser PJ
FAU - Whittington, Catherine
AU  - Whittington C
FAU - Voytik-Harbin, Sherry L
AU  - Voytik-Harbin SL
FAU - Yoder, Mervin C
AU  - Yoder MC
LA  - eng
GR  - R01 HL109602/HL/NHLBI NIH HHS/United States
GR  - R01HL10962/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140223
PL  - Germany
TA  - Angiogenesis
JT  - Angiogenesis
JID - 9814575
RN  - 0 (ANGPTL2 protein, human)
RN  - 0 (Angiopoietin-Like Protein 2)
RN  - 0 (Angiopoietin-like Proteins)
RN  - 0 (Angiopoietins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.4.24.80 (MMP14 protein, human)
RN  - EC 3.4.24.80 (Matrix Metalloproteinase 14)
SB  - IM
MH  - Angiopoietin-Like Protein 2
MH  - Angiopoietin-like Proteins
MH  - Angiopoietins/genetics/*metabolism/pharmacology
MH  - Cell Migration Assays
MH  - Cell Movement/drug effects
MH  - Colony-Forming Units Assay
MH  - Endothelial Cells/*cytology/drug effects/enzymology/*metabolism
MH  - Gene Expression Regulation/drug effects
MH  - Gene Silencing/drug effects
MH  - Humans
MH  - JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism
MH  - Matrix Metalloproteinase 14/genetics/metabolism
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - *Neovascularization, Physiologic/drug effects/genetics
MH  - Phosphorylation/drug effects
MH  - RNA, Messenger/genetics/metabolism
MH  - Recombinant Proteins/pharmacology
MH  - Signal Transduction/drug effects
PMC - PMC4063876
MID - NIHMS569794
EDAT- 2014/02/25 06:00
MHDA- 2015/02/05 06:00
PMCR- 2015/07/01
CRDT- 2014/02/25 06:00
PHST- 2013/07/22 00:00 [received]
PHST- 2014/02/17 00:00 [accepted]
PHST- 2014/02/25 06:00 [entrez]
PHST- 2014/02/25 06:00 [pubmed]
PHST- 2015/02/05 06:00 [medline]
PHST- 2015/07/01 00:00 [pmc-release]
AID - 10.1007/s10456-014-9423-8 [doi]
PST - ppublish
SO  - Angiogenesis. 2014 Jul;17(3):675-83. doi: 10.1007/s10456-014-9423-8. Epub 2014 
      Feb 23.