Age-related changes in the liver sinusoidal endothelium: a mechanism for dyslipidemia.
The liver sinusoidal endothelial cell (LSEC) influences the transfer of substrates between the sinusoidal blood and hepatocytes and has a major role in endocytosis; therefore, changes in the LSEC have significant implications for hepatic function. There are major morphological changes in the LSEC in old age called pseudocapillarization. These changes include increased LSEC thickness and reduced numbers of pores in the LSEC, which are called fenestrations. Pseudocapillarization has been found in old humans, rats, mice, and nonhuman primates. In addition, old age is associated with impaired LSEC endocytosis and increased leukocyte adhesion, which contributes to reduced hepatic perfusion. Given that fenestrations in the endothelium allow passage of some lipoproteins, including chylomicron remnants, age-related reduction in fenestrations impairs hepatic lipoprotein metabolism. In old rats, caloric restriction was associated with complete preservation of LSEC morphology and fenestrations. In conclusion, pseudocapillarization of the LSEC is a newly discovered aging change that, through its effects on lipoproteins, contributes to the association between old age, dyslipidemia, and vascular disease.
LE Couteur
David G
DG
Centre for Education and Research on Ageing, University of Sydney and Concord RG Hospital, Sydney, NSW 2139, Australia. dlecouteur@med.usyd.edu.au
Cogger
Victoria C
VC
McCuskey
Robert S
RS
DE Cabo
Rafael
R
Smedsrød
Bârd
B
Sorensen
Karen K
KK
Warren
Alessandra
A
Fraser
Robin
R
D000375:Aging / Q000097:blood / Q000473:pathology*; D000818:Animals; D050171:Dyslipidemias / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D008099:Liver / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology