The Interpretation of Cholesterol Balance Derived Synthesis Data and Surrogate Noncholesterol Plasma Markers for Cholesterol Synthesis under Lipid Lowering Therapies.
The cholesterol balance procedure allows the calculation of cholesterol synthesis based on the assumption that loss of endogenous cholesterol via fecal excretion and bile acid synthesis is compensated byde novosynthesis. Under ezetimibe therapy hepatic cholesterol is diminished which can be compensated by hepaticde novosynthesis and hepatic extraction of plasma cholesterol. The plasma lathosterol concentration corrected for total cholesterol concentration (R_Lath) as a marker ofde novocholesterol synthesis is increased during ezetimibe treatment but unchanged under treatment with ezetimibe and simvastatin. Cholesterol balance derived synthesis data increase during both therapies. We hypothesize the following. (1) The cholesterol balance data must be applied to the hepatobiliary cholesterol pool. (2) The calculated cholesterol synthesis value is the sum of hepaticde novosynthesis and the net plasma-liver cholesterol exchange rate. (3) The reduced rate of biliary cholesterol absorption is the major trigger for the regulation of hepatic cholesterol metabolism under ezetimibe treatment. Supportive experimental and literature data are presented that describe changes of cholesterol fluxes under ezetimibe, statin, and combined treatments in omnivores and vegans, link plasma R_Lath to liver function, and define hepaticde novosynthesis as target for regulation of synthesis. An ezetimibe dependent direct hepatic drug effect cannot be excluded.
Institute for Clinical Chemistry and Clinical Pharmacology, University Clinics of Bonn, Bonn, Germany.
Frans
F
Stellaard
Institute for Clinical Chemistry and Clinical Pharmacology, University Clinics of Bonn, Bonn, Germany.
Dieter
0000-0002-7941-8308
D
Lütjohann