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.