Hepatic sinusoidal endothelial cell G1/S arrest correlates with severity of alcoholic liver injury in the rat.
OBJECTIVE
Capillarization of the hepatic sinusoid occurs in alcoholic liver disease. Because endothelial cell proliferation is relevant to capillarization, we used the intragastric feeding rat model to evaluate the relationship between pathological liver injury and endothelial cell proliferation.


METHODS
Male Wistar rats (225-250 g) were fed liquid diets containing corn oil and ethanol for periods ranging between 1 week and 2 months. At the time the rats were killed, the severity of pathological injury and endothelial cell proliferation using anti-rat proliferating cell nuclear antigen/antibody was evaluated.


RESULTS
Two distinctly different populations of proliferating sinusoidal lining cells were identified; one population showed relatively weak granular staining consistent with cells arrested at the G1/S boundary. The other population of cells showed strong granular staining of the nucleoplasm and nucleoli (cells in mid to late S phase). A strong correlation (r = 0.85; P < 0.01) was obtained between pathological severity and G1/S-arrested endothelial cells. There was no correlation between cells in S phase.


CONCLUSIONS
The presence of an increased number of G1/S-arrested endothelial cells in animals with severe pathological change suggests that stimuli are present for both endothelial cell proliferation and G1/arrest. The identification of these stimuli could lead to a better understanding of the pathogenesis of alcoholic liver disease.
Nanji
A A
AA
Department of Pathology, New England Deaconess Hospital, Boston, Massachusetts.
Tahan
S R
SR
Wei
Y
Y
Sadrzadeh
S M
SM
D000818:Animals; D002455:Cell Division; D003314:Corn Oil / Q000008:administration & dosage; D004032:Diet; D004727:Endothelium / Q000378:metabolism / Q000473:pathology; D000431:Ethanol / Q000008:administration & dosage; D016193:G1 Phase; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008108:Liver Diseases, Alcoholic / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009687:Nuclear Proteins / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen; D051381:Rats; D017208:Rats, Wistar; D016196:S Phase
D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D000431:Ethanol; D003314:Corn Oil