Main |
Browse Volumes |
Forthcoming Volumes |
Annals PrePrints |
Annals Extra |
E-mail Alerts |
Subscriptions & Orders |
New Proposals |
Author Guidelines |
About Annals |
Help |
 |
|
|
|
|
|
Age-Related Changes in the Liver Sinusoidal EndotheliumA Mechanism for Dyslipidemia
DAVID G. LE COUTEURa,
VICTORIA C. COGGERa,
ROBERT S. MCCUSKEYbc,
RAFAEL DE CABOd,
BÂRD SMEDSRØDc,
KAREN K. SORENSENc,
ALESSANDRA WARRENa AND
ROBIN FRASERe
a Centre for Education and Research on Ageing, University of Sydney and Concord RG Hospital, Sydney, NSW, Australia b Department of Cell Biology and Anatomy, College of Medicine, University of Arizona, Tucson, Arizona, USA c Department of Cell Biology and Histology, Institute of Medical Biology, University of Tromso, Tromso, Norway d Laboratory of Experimental Gerontology, National Institute on Aging, Baltimore, Maryland, USA e Christchurch School of Medicine, University of Otago, Christchurch, New Zealand
Key Words: liver • aging • liver sinusoidal endothelial cell • chylomicron remnant • endocytosis • caloric restriction
Address for correspondence: Professor David G. Le Couteur, Centre for Education and Research on Ageing, University of Sydney and Concord RG Hospital, Sydney, NSW 2139, Australia. Voice: +612-9767-7212; fax: +612-9767-5419. dlecouteur{at}med.usyd.edu.au
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.
|
