Transcriptional and posttranscriptional regulation of apolipoprotein E, A-I, and A-II gene expression in normal rat liver and during several pathophysiologic states

Assessment of the relative transcription rates and mRNA steady-state levels for apolipoprotein genes E, A-I, and A-II has been performed in normal rat liver, during liver regeneration and following induction of cirrhosis, as well as in rats with inherited analbuminemia associated with hyperlipidemia. Apo E exhibits primarily transcriptional control with an additional component of posttranscriptional control, whereas Apo A-I is controlled primarily at the posttranscriptional level, thus indicating that these genes are regulated independently. The level of control for Apo A-II has not been determined, because of difficulty experienced in measuring the transcription rate of this gene. During liver regeneration, cirrhosis, and analbuminemia, there is a marked increase in the ratio of Apo A-I to Apo E mRNA, resulting from an increase in the Apo A-I mRNA steady-state level and a decrease in Apo E mRNA. These changes are similar in the three pathophysiologic states and seem to occur through a combination of transcriptional and posttranscriptional mechanisms.