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Aging and the Hepatic Sinusoidal Endothelium
Author(s) -
Le Couteur David G
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.66.4
Subject(s) - perisinusoidal space , hepatic stellate cell , sinusoid , basal lamina , biology , endocrinology , pathology , lipid droplet , cirrhosis , endothelium , medicine , chemistry , hepatocyte , microbiology and biotechnology , ultrastructure , biochemistry , in vitro
Old age in many species including humans is associated with substantial thickening and defenestration of the liver sinusoidal endothelial cell, sporadic deposition of collagen and basal lamina in the extracellular space of Disse and increased numbers of fat engorged, non‐activated stellate cells. Associated immunohistochemical age‐related changes include peri‐sinusoidal upregulation of von Willebrands factor, VEGFR‐2, collagen I and IV and ICAM‐1. There is also a small reduction in the fractal dimension of the microvascular architecture but without any change in vascular dispersion. On the other hand, unlike most liver disease, there is no change in expression of alpha‐SMA, desmin or VEGF, reduced expression of caveolin‐1 and stellate cells are not activated. These age‐related changes have been termed pseudocapillarization in order to differentiate them from capillarization seen in cirrhosis. Pseudocapillarization is reversed by caloric restriction indicating it is likely to be a primary aging change. There is an associated impairment of endocytosis. In aged rats the loss of fenestrations leads to impaired transfer of lipoproteins from the sinusoid into the space of Disse. This provides a novel mechanism and therapeutic target for impaired chylomicron remnant clearance and post‐prandial hyperlipidemia associated with old age.