HYPERCHOLESTEROLEMIA INDUCES DIFFERENTIAL EXPRESSION OF RABBIT APOLIPOPROTEIN-A-GENE AND APOLIPOPROTEIN-C-GENE

We have compared steady-state mRNA levels of apolipoproteins AI, AII, AIV, Cl, CII and CIII in liver and small intestine of rabbits fed on a cholesterol-rich diet for up to 16 weeks. Apolipoprotein (apo) AIV mRNA was detected in both liver and small intestine, while apo AII was not detected in either organ. Apo CI, apo CII and apo CIII were expressed only in liver and apo AI mRNA was detected only in small intestine. In small intestine, apo AIV and apo AI mRNA levels increased to a maximum at the 4th and 12th week of treatment, respectively. In liver there was a parallel increase in the mRNA levels of apo AIV, apo CI, apo CII and apo CIII, with maximum levels after 4 weeks of treatment. A 3-fold increase was found in apo CII and apo CIII hepatic transcription rates between hypercholesterolemic and control rabbits after 4 weeks of treatment, no longer detectable after 8 weeks. However, no changes were found in apo AIV and apo CI transcription rates. Changes in apolipoprotein mRNA levels were accompanied by changes in plasma lipoprotein levels. Overall, these changes correlate well with the variations detected in the expression of the different apolipoprotein genes. Our results indicate that dietary cholesterol plays an important role in the regulation of these genes and that this regulation is tissue dependent.