PMID- 20875806
OWN - NLM
STAT- MEDLINE
DCOM- 20110321
LR  - 20211020
IS  - 1872-6240 (Electronic)
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 1366
DP  - 2010 Dec 17
TI  - Hypoxia-inducible factor-1 (HIF-1)-independent microvascular angiogenesis in the 
      aged rat brain.
PG  - 101-9
LID - 10.1016/j.brainres.2010.09.064 [doi]
AB  - Angiogenesis is a critical component of mammalian brain adaptation to prolonged 
      hypoxia. Hypoxia-induced angiogenesis is mediated by hypoxia-inducible factor-1 
      (HIF-1)-dependent transcriptional activation of growth factors, such as vascular 
      endothelial growth factor (VEGF). Microvascular angiogenesis occurs over a 3-week 
      period in the rodent brain. We have recently reported that HIF-1alpha accumulation 
      and transcriptional activation of HIF target genes in the aged cortex of 
      24-month-old F344 rats is significantly attenuated during acute hypoxic exposure. 
      In the present study, we show that cortical HIF-1alpha accumulation and HIF-1 
      activation remain absent during chronic hypoxic exposure in the aged rat brain 
      (24-month-old F344). Despite this lack of HIF-1 activation, there is no 
      significant difference in baseline or post-hypoxic brain capillary density counts 
      between the young (3-month-old F344) and old age groups. VEGF mRNA and protein 
      levels are significantly elevated in the aged cortex despite the lack of HIF-1 
      activation. Other HIF-independent mediators of hypoxia-inducible genes could be 
      involved during chronic hypoxia in the aged brain. PPAR-gamma coactivator (PGC)-1alpha, a 
      known regulator of VEGF gene transcription, is elevated in the young and aged 
      cortex during the chronic hypoxic exposure. Overall, our results suggest a 
      compensatory HIF-1-independent preservation of hypoxic-induced microvascular 
      angiogenesis in the aged rat brain.
CI  - Copyright (c) 2010 Elsevier B.V. All rights reserved.
FAU - Ndubuizu, Obinna I
AU  - Ndubuizu OI
AD  - Department of Physiology and Biophysics, Case Western Reserve University, School 
      of Medicine, 10900 Euclid Avenue BRB 501A, Cleveland, OH 44106-4930, USA. 
      oin@case.edu
FAU - Tsipis, Constantinos P
AU  - Tsipis CP
FAU - Li, Ang
AU  - Li A
FAU - LaManna, Joseph C
AU  - LaManna JC
LA  - eng
GR  - T32 GM007250-23/GM/NIGMS NIH HHS/United States
GR  - R01 HL092933/HL/NHLBI NIH HHS/United States
GR  - T32 GM007250/GM/NIGMS NIH HHS/United States
GR  - R01 NS038632-12/NS/NINDS NIH HHS/United States
GR  - R01 NS038632/NS/NINDS NIH HHS/United States
PT  - Journal Article
DEP - 20100925
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Glucose Transporter Type 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
RN  - 0 (Ppargc1a protein, rat)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (Slc2a1 protein, rat)
RN  - 0 (Transcription Factors)
RN  - 0 (Vascular Endothelial Growth Factor A)
SB  - IM
MH  - Age Factors
MH  - *Aging
MH  - Animals
MH  - Brain/pathology/*physiopathology
MH  - Glucose Transporter Type 1/metabolism
MH  - Hypoxia/*pathology/physiopathology
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism
MH  - Neovascularization, Pathologic/*physiopathology
MH  - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
MH  - RNA, Messenger/metabolism
MH  - RNA-Binding Proteins/metabolism
MH  - Rats
MH  - Rats, Inbred F344
MH  - Time Factors
MH  - Transcription Factors/metabolism
MH  - Up-Regulation/physiology
MH  - Vascular Endothelial Growth Factor A/genetics/*metabolism
PMC - PMC3378376
MID - NIHMS252102
EDAT- 2010/09/30 06:00
MHDA- 2011/03/22 06:00
PMCR- 2012/06/19
CRDT- 2010/09/30 06:00
PHST- 2010/04/21 00:00 [received]
PHST- 2010/08/30 00:00 [revised]
PHST- 2010/09/17 00:00 [accepted]
PHST- 2010/09/30 06:00 [entrez]
PHST- 2010/09/30 06:00 [pubmed]
PHST- 2011/03/22 06:00 [medline]
PHST- 2012/06/19 00:00 [pmc-release]
AID - S0006-8993(10)02130-X [pii]
AID - 10.1016/j.brainres.2010.09.064 [doi]
PST - ppublish
SO  - Brain Res. 2010 Dec 17;1366:101-9. doi: 10.1016/j.brainres.2010.09.064. Epub 2010 
      Sep 25.