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The 187th Meeting of the Pathological Society of Great Britain and Ireland, The Robin Brook Centre, St. Bartholomew's Hospital, London, 6–7 January 2005
Author(s) -
So, H,
Lau, THY,
Tipoe, GL,
Liao, LC,
Liong, EC,
Nanji, AA,
Leung, KM,
Fung, ML
Publication year - 2005
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1762
Subject(s) - citation , library science , history , genealogy , computer science
We determined the hepatic expression of transcriptional factor HIF-1α inhypoxia and genes possessing hypoxia response element (HRE) such as iNOS,VEGF and ET-1 that modulate the vascular response in liver. We also evaluatedthe concomitant expressions of NF-κB and AP-1. Blood and liver samples fromadult SD rats were collected at specific time-points after exposure of animals to10% oxygen for a period of 28 days. Samples from the normoxic and hypoxicrats were analyzed for serum ALT, hematocrit, 8-isoprostane,immunohistochemistry, RT-PCR, Western Blotting and EMSA.Our results showed a significant increase in the hematocrit and asignificant weight loss in the hypoxic rats. The liver morphology and serumALT were normal. Total free 8-isoprostane levels and nitrotyrosine proteinwere not elevated. iNOS mRNA peaked at day 21 whereas eNOS, VEGF andET-1 mRNAs progressively increased from day 7 to day 28 in hypoxic liver.Similar trends were observed at the protein level by Western blotting. HIF-1α,NF-κB and AP-1 were upregulated in hypoxic liver. We conclude that thevascular adaptive ability of the liver in chronic hypoxia triggers compensatorynitric oxide-dependent mechanisms for cell survival towards a vasodilatoryresponse through upregulation of transcription factors, HRE and eNOS geneslink_to_subscribed_fulltex