PMID- 10702412
OWN - NLM
STAT- MEDLINE
DCOM- 20000323
LR  - 20210109
IS  - 0002-9440 (Print)
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Linking)
VI  - 156
IP  - 3
DP  - 2000 Mar
TI  - Hypoxia-induced vascular endothelial growth factor expression precedes 
      neovascularization after cerebral ischemia.
PG  - 965-76
AB  - We investigated the hypothesis that hypoxia induces angiogenesis and thereby may 
      counteract the detrimental neurological effects associated with stroke. 
      Forty-eight to seventy-two hours after permanent middle cerebral artery occlusion 
      we found a strong increase in the number of newly formed vessels at the border of 
      the infarction. Using the hypoxia marker nitroimidazole EF5, we detected hypoxic 
      cells in the ischemic border of the neocortex. Expression of vascular endothelial 
      growth factor (VEGF), which is the main regulator of angiogenesis and is 
      inducible by hypoxia, was strongly up-regulated in the ischemic border, at times 
      between 6 and 24 hours after occlusion. In addition, both VEGF receptors (VEGFRs) 
      were up-regulated at the border after 48 hours and later in the ischemic core. 
      Finally, the two transcription factors, hypoxia-inducible factor-1 (HIF-1) and 
      HIF-2, known to be involved in the regulation of VEGF and VEGFR gene expression, 
      were increased in the ischemic border after 72 hours, suggesting a regulatory 
      function for these factors. These results strongly suggest that the VEGF/VEGFR 
      system, induced by hypoxia, leads to the growth of new vessels after cerebral 
      ischemia. Exogenous support of this natural protective mechanism might lead to 
      enhanced survival after stroke.
FAU - Marti, H J
AU  - Marti HJ
AD  - Department of Molecular Cell Biology, the Max Planck Institute for Physiological 
      and Clinical Research, Bad Nauheim, Germany. hugo.marti@kerckhoff.mpg.de
FAU - Bernaudin, M
AU  - Bernaudin M
FAU - Bellail, A
AU  - Bellail A
FAU - Schoch, H
AU  - Schoch H
FAU - Euler, M
AU  - Euler M
FAU - Petit, E
AU  - Petit E
FAU - Risau, W
AU  - Risau W
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (DNA Primers)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Endothelial Growth Factors)
RN  - 0 (HIF-2 protein, mouse)
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Ki-67 Antigen)
RN  - 0 (Lymphokines)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Peptide Initiation Factors)
RN  - 0 (Platelet Endothelial Cell Adhesion Molecule-1)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Growth Factor)
RN  - 0 (Transcription Factors)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (Vascular Endothelial Growth Factors)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptors, Vascular Endothelial Growth Factor)
RN  - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-1)
SB  - IM
MH  - Animals
MH  - Brain Ischemia/*complications/metabolism/pathology
MH  - DNA/analysis
MH  - DNA Primers/chemistry
MH  - DNA-Binding Proteins/metabolism
MH  - Disease Models, Animal
MH  - Endothelial Growth Factors/genetics/*metabolism
MH  - Hypoxia/*complications/metabolism/pathology
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Immunohistochemistry
MH  - In Situ Hybridization
MH  - Ki-67 Antigen/metabolism
MH  - Lymphokines/genetics/*metabolism
MH  - Mice
MH  - Neovascularization, Pathologic/*etiology/metabolism/pathology
MH  - Nuclear Proteins/metabolism
MH  - Peptide Initiation Factors/metabolism
MH  - Platelet Endothelial Cell Adhesion Molecule-1/metabolism
MH  - Proto-Oncogene Proteins/genetics/metabolism
MH  - RNA, Messenger/metabolism
MH  - Receptor Protein-Tyrosine Kinases/genetics/metabolism
MH  - Receptors, Growth Factor/genetics/metabolism
MH  - Receptors, Vascular Endothelial Growth Factor
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transcription Factors/biosynthesis
MH  - Up-Regulation
MH  - Vascular Endothelial Growth Factor A
MH  - Vascular Endothelial Growth Factor Receptor-1
MH  - Vascular Endothelial Growth Factors
PMC - PMC1876841
EDAT- 2000/03/07 09:00
MHDA- 2000/03/25 09:00
PMCR- 2000/09/01
CRDT- 2000/03/07 09:00
PHST- 2000/03/07 09:00 [pubmed]
PHST- 2000/03/25 09:00 [medline]
PHST- 2000/03/07 09:00 [entrez]
PHST- 2000/09/01 00:00 [pmc-release]
AID - S0002-9440(10)64964-4 [pii]
AID - 2091 [pii]
AID - 10.1016/S0002-9440(10)64964-4 [doi]
PST - ppublish
SO  - Am J Pathol. 2000 Mar;156(3):965-76. doi: 10.1016/S0002-9440(10)64964-4.