Bile acids and lipoprotein metabolism: Effects of cholestyramine and chenodeoxycholic acid on human hepatic mRNA expression

Modulation of bile acid synthesis in human by cholestyramine or by chenodeoxycholic acid (CDCA) treatment affects lipoprotein metabolism leading to altered plasma lipid levels. The molecular changes caused by these treatments, which in turn influence lipoprotein metabolism, are still not entirely known in humans. In this study, mRNA levels were analyzed using real time RT-PCR in liver tissue from patients undergoing cholecystectomy due to gallstone disease. The patients were treated with either CDCA (n = 6) or cholestyramine (n = 5) for three weeks prior to surgery, six patients received no treatment and served as controls. Cholestyramine increased the expression of the LDL receptor (LDLR) by about 65% and that of proprotein convertase subtilisin kexin 9 (PCSK9) by 70%. After CDCA the levels of both LDLR and hydroxy-methyl-glutaryl coenzyme A reductase mRNA decreased approximately by 50%. The expression of PCSK9 was not changed. The mRNA levels of PCSK9, LDLR, and HMGCoAR were significantly correlated to those of sterol regulatory element binding protein 2 (SREBP2), indicating that SREBP2 is of importance in the regulation of the expression of these genes also in human liver. (C) 2007 Elsevier Inc. All rights reserved.