PMID- 26678600
OWN - NLM
STAT- MEDLINE
DCOM- 20161219
LR  - 20190424
IS  - 1573-7209 (Electronic)
IS  - 0969-6970 (Linking)
VI  - 19
IP  - 2
DP  - 2016 Apr
TI  - Suppression of vascular network formation by chronic hypoxia and 
      prolyl-hydroxylase 2 (phd2) deficiency during vertebrate development.
PG  - 119-31
LID - 10.1007/s10456-015-9492-3 [doi]
AB  - In the adult, new vessels and red blood cells form in response to hypoxia. Here, 
      the oxygen-sensing system (PHD-HIF) has recently been put into focus, since the 
      prolyl-hydroxylase domain proteins (PHD) and hypoxia-inducible factors (HIF) are 
      considered as potential therapeutic targets to treat ischemia, cancers or 
      age-related macula degeneration. While the oxygen-sensing system (PHD-HIF) has 
      been studied intensively in this respect, only little is known from developing 
      vertebrate embryos since mutations within this pathway led to an early decease of 
      embryos due to placental defects. During vertebrate embryogenesis, a progenitor 
      cell called hemangioblast is assumed to give rise to blood cells and blood 
      vessels in a process called hematopoiesis and vasculogenesis, respectively. 
      Xenopus provides an ideal experimental system to address these processes in vivo, 
      as its development does not depend on a functional placenta and thus allows 
      analyzing the role of oxygen directly. To this end, we adopted a 
      computer-controlled four-channel system, which allowed us to culture Xenopus 
      embryos under defined oxygen concentrations. Our data show that the development 
      of vascular structures and blood cells is strongly impaired under hypoxia, while 
      general development is less compromised. Interestingly, suppression of Phd2 
      function using specific antisense morpholinos or a chemical inhibitor resulted in 
      mostly overlapping vascular defects; nevertheless, blood cell was formed almost 
      normally. Our results provide the first evidence that oxygen via Phd2 has a 
      decisive influence on the formation of the vascular network during vertebrate 
      embryogenesis. These findings may be considered in certain potential treatment 
      concepts.
FAU - Metikala, Sanjeeva
AU  - Metikala S
AD  - Department of Medical Molecular Biology, Medical Faculty, Institute for 
      Physiological Chemistry, Martin-Luther-University Halle-Wittenberg, Hollystrasse 
      1, 06114, Halle (Saale), Germany.
FAU - Neuhaus, Herbert
AU  - Neuhaus H
AD  - Department of Medical Molecular Biology, Medical Faculty, Institute for 
      Physiological Chemistry, Martin-Luther-University Halle-Wittenberg, Hollystrasse 
      1, 06114, Halle (Saale), Germany.
FAU - Hollemann, Thomas
AU  - Hollemann T
AD  - Department of Medical Molecular Biology, Medical Faculty, Institute for 
      Physiological Chemistry, Martin-Luther-University Halle-Wittenberg, Hollystrasse 
      1, 06114, Halle (Saale), Germany. thomas.hollemann@medizin.uni-halle.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151217
PL  - Germany
TA  - Angiogenesis
JT  - Angiogenesis
JID - 9814575
RN  - 0 (Xenopus Proteins)
RN  - EC 1.14.11.- (EGLN1 protein, Xenopus)
RN  - EC 1.14.11.- (Prolyl Hydroxylases)
RN  - EC 1.14.11.2 (Procollagen-Proline Dioxygenase)
SB  - IM
MH  - Animals
MH  - Blood Cells/metabolism
MH  - Blood Vessels/*embryology
MH  - Cell Differentiation
MH  - Cell Lineage
MH  - Chronic Disease
MH  - *Embryonic Development
MH  - Hematopoiesis
MH  - Hypoxia/embryology/*pathology
MH  - *Neovascularization, Physiologic
MH  - Procollagen-Proline Dioxygenase/*deficiency/metabolism
MH  - Prolyl Hydroxylases/*metabolism
MH  - Xenopus Proteins/*metabolism
MH  - Xenopus laevis/*embryology/*physiology
OTO - NOTNLM
OT  - Angiogenesis
OT  - Hypoxia
OT  - Prolyl-hydroxylase domain
OT  - Vasculogenesis
OT  - Xenopus
OT  - phd2
EDAT- 2015/12/19 06:00
MHDA- 2016/12/20 06:00
CRDT- 2015/12/19 06:00
PHST- 2015/06/17 00:00 [received]
PHST- 2015/12/08 00:00 [accepted]
PHST- 2015/12/19 06:00 [entrez]
PHST- 2015/12/19 06:00 [pubmed]
PHST- 2016/12/20 06:00 [medline]
AID - 10.1007/s10456-015-9492-3 [pii]
AID - 10.1007/s10456-015-9492-3 [doi]
PST - ppublish
SO  - Angiogenesis. 2016 Apr;19(2):119-31. doi: 10.1007/s10456-015-9492-3. Epub 2015 
      Dec 17.