PMID- 16842206
OWN - NLM
STAT- MEDLINE
DCOM- 20060811
LR  - 20191110
IS  - 1871-5257 (Print)
IS  - 1871-5257 (Linking)
VI  - 4
IP  - 3
DP  - 2006 Jul
TI  - Expression and functions of vasoactive substances regulated by hypoxia-inducible 
      factor-1 in chronic hypoxemia.
PG  - 199-218
AB  - The aims of the present review are to summarize and to discuss the role of 
      hypoxia-inducible factor-1 (HIF-1) and the expression and functions of vasoactive 
      substances in chronic hypoxemia with specific focus in the liver and the carotid 
      body. Vascular remodelling and vasoactive substances play important functional 
      roles in the adaptive response to chronic hypoxemia for the maintenance of oxygen 
      homeostasis in all systems in man. HIF-1 regulates the gene expression of 
      vasoactive substances such as vascular endothelial growth factor (VEGF), 
      endothelin-1 (ET-1) and enzymes for producing nitric oxide (NO). Recent studies 
      have shown the effect of chronic hypoxia on the expression of HIF-1alpha and 
      HIF-1-target genes in multiple organ systems including the liver and the carotid 
      body. Results are consistent with increases in the hematocrit levels, pulmonary 
      arterial pressure and right heart mass developed during chronic hypoxia. In 
      addition, the carotid body is also hyperplastic and increases in organ mass with 
      increased levels of HIF-1alpha and the vasoactive substances. These molecules 
      increase the mitotic activity and modulate the excitability of the chemoreceptor. 
      Intriguingly, the liver morphology, serum alanine aminotransferase and 
      8-isoprostane levels are within normal range in chronic hypoxia, suggesting the 
      absence of significant oxidative stress. Yet, the HIF-1alpha is upregulated and 
      the mRNA and protein levels of VEGF, ET-1, inducible and constitutive NO 
      synthases are elevated in the liver during chronic hypoxia. In conclusion, the 
      adaptive response to long-term hypoxemia involves compensatory mechanisms 
      mediated by expressing significant levels of HIF-1alpha and vasoactive substances 
      regulated by HIF-1.
FAU - Tipoe, George L
AU  - Tipoe GL
AD  - Department of Anatomy, The University of Hong Kong, Pokfulam, Hong Kong SAR, 
      China.
FAU - Lau, Thomas Y-H
AU  - Lau TY
FAU - Nanji, Amin A
AU  - Nanji AA
FAU - Fung, Man-Lung
AU  - Fung ML
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - Netherlands
TA  - Cardiovasc Hematol Agents Med Chem
JT  - Cardiovascular & hematological agents in medicinal chemistry
JID - 101266881
RN  - 0 (Endothelin-1)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Transcription Factors)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 11096-26-7 (Erythropoietin)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Animals
MH  - Carotid Arteries/metabolism
MH  - Chronic Disease
MH  - Endothelin-1/metabolism/physiology
MH  - Erythropoietin/metabolism/physiology
MH  - Humans
MH  - Hypoxia/genetics/*physiopathology
MH  - Hypoxia-Inducible Factor 1/genetics/*physiology
MH  - Liver/physiopathology
MH  - Nitric Oxide/metabolism/physiology
MH  - Oxygen/metabolism
MH  - Transcription Factors/metabolism/physiology
MH  - Vascular Endothelial Growth Factor A/metabolism/physiology
RF  - 250
EDAT- 2006/07/18 09:00
MHDA- 2006/08/12 09:00
CRDT- 2006/07/18 09:00
PHST- 2006/07/18 09:00 [pubmed]
PHST- 2006/08/12 09:00 [medline]
PHST- 2006/07/18 09:00 [entrez]
AID - 10.2174/187152506777698290 [doi]
PST - ppublish
SO  - Cardiovasc Hematol Agents Med Chem. 2006 Jul;4(3):199-218. doi: 
      10.2174/187152506777698290.