HYPOCHOLESTEROLEMIC EFFECTS OF THE LDL RECEPTOR GENE TRANSCRIPTIONAL UPREGULATOR CP-230821

CP-230821 is a novel, potent LDL receptor gene transcriptional upregul ator which decreases total plasma cholesterol level, Interestingly, th is plasma LDL decrease does not alter hepatic lipid contents. A series of experiments mas undertaken to study the molecular biology of this phenomenon, Twelve hours after CP-230821 treatment, the transcriptiona l activity and mRNA level of the LDL receptor gene in HepG2 cells were increased by 264% and 426%, respectively, Although treatment with the HMG-CoA reductase inhibitor compactin also increased LDL receptor gen e transcription and mRNA, CP-230821 did not increase the level of HMG- CoA reductase gene transcription or mRNA, These results indicate that LDL receptor gene activity may play an important role in the decrease of plasma LDL level. These results further suggest that the LDL recept or gene and the HMG-CoA reductase gene are not strictly coordinately c ontrolled.