Cholesterol-induced stimulation of postinflammatory liver fibrosis.
We studied the effect of high-cholesterol diet and factors inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase on the development of liver fibrosis in C57Bl/6 mice with CCl4- or zymosan-induced hepatitis. Feeding a high-cholesterol diet led to a sharp increase in collagen content in the liver tissue of animals with CCl4-induced or zymosan-induced hepatitis. Atorvastatin and calcitriol produced less pronounced fibrogenic effects. Mevalonate partially prevented the development of cholesterol-induced fibrogenesis. High-cholesterol diet led to accumulation of oxysterols, cholesterol esters, and triglycerides and increased the expression of transforming growth factor-beta1 mRNA in liver tissue. Cholesterol-induced potentiation of the fibrogenic response is probably associated with transforming growth factor-beta1 induction due to accumulation of lipids and oxysterols in the liver.
Schwartz
Y Sh
YSh
Institute of Therapy, Siberian Division of the Russian Academy of Medical Sciences, Novosibirsk. Russia. yshschwartz@mail.ru
Dushkin
M I
MI
Komarova
N I
NI
Vorontsova
E V
EV
Kuznetsova
I S
IS
D000818:Animals; D000069059:Atorvastatin; D002117:Calcitriol / Q000494:pharmacology; D002788:Cholesterol Esters / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D003094:Collagen / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006538:Heptanoic Acids / Q000494:pharmacology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D008297:Male; D008798:Mevalonic Acid / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D011758:Pyrroles / Q000494:pharmacology; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D014280:Triglycerides / Q000378:metabolism; D015054:Zymosan / Q000494:pharmacology
D002788:Cholesterol Esters; D002791:Cholesterol, Dietary; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1; D014280:Triglycerides; D003094:Collagen; D015054:Zymosan; D000069059:Atorvastatin; D002117:Calcitriol; D008798:Mevalonic Acid