The effect of old age on liver oxygenation and the hepatic expression of VEGF and VEGFR2.
In old age, the liver contains less ATP and hypoxia-responsive genes are upregulated. Age-related changes in hepatic perfusion and the liver sinusoidal endothelial cell (LSEC) could contribute to this altered hepatic oxygen-dependent metabolism by causing intrahepatocytic hypoxia. Furthermore, age-related changes in the LSEC ('pseudocapillarization') have been partially induced by ATP depletion. To investigate whether there is intracellular hypoxia in the old rat liver, pimonidazole immunohistochemistry in intact livers and ATP levels in isolated LSECs were studied from young and old rats. There were no age-related changes. To determine whether defenestration of the LSEC could impair oxygen diffusion, pimonidazole immunohistochemistry was performed in rats treated with poloxamer 407. Despite defenestration, there was no change in pimonidazole staining. Immunohistochemistry was then performed to determine whether there are age-related changes in VEGF and VEGFR2. VEGF staining was not associated with age. However, there was an increase in perisinusoidal VEGFR2 expression with increasing age. In conclusion, liver hypoxia does not occur in old age and LSEC pseudocapillarization does not constitute an oxygen-diffusion barrier. There are no age-related changes in VEGF expression but an increase in perisinusoidal VEGFR2 expression, which has implications for the effects of aging on the hepatic sinusoid.
Centre for Education and Research on Ageing and ANZAC Research Institute, University of Sydney, Concord RG Hospital, Concord, NSW 2139, Australia. rcheluvappa@med.usyd.edu.au
Rajkumar
R
Cheluvappa
Sarah N
SN
Hilmer
Sun Young
SY
Kwun
Hamish A
HA
Jamieson
Jennifer N
JN
O'Reilly
Michael
M
Muller
Victoria C
VC
Cogger
David G
DG
Le Couteur
D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D007124:Immunoenzyme Techniques; D008099:Liver / Q000378:metabolism* / Q000648:ultrastructure; D008102:Liver Circulation / Q000502:physiology; D008297:Male; D008855:Microscopy, Electron, Scanning; D010101:Oxygen Consumption / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D040301:Vascular Endothelial Growth Factor Receptor-2