Maternal hypercholesterolemia leads to activation of endogenous cholesterol synthesis in the offspring

Objective: The purpose of this study was to determine the effect of maternal hypercholesterolemia on hepatic cholesterol metabolism in the offspring in a mouse model. Study Design: Male and female wild type and apoE^-/-KO (knockout for the apoprotein E [apoE]) gene) mice were crossbred to obtain all 4 possible genetic offspring types. The litters were maintained on regular chow and sacrificed at 8 months of age. Liver samples were collected and the mRNA expression levels for SCAP, SREBP-1a, SREBP-2, HMGCR, and LDLR determined using real-time RT-PCR. Results: We found a significant activation of the transcriptional activity of genes involved in endogenous cholesterol synthesis, as well as LDLR, in the liver of adult mice born to hypercholesterolemic dams. Conclusion: Reprogramming of hepatic cholesterol homeostasis may be the basis for an increased predisposition to hypercholesterolemia and atherosclerosis found in offspring of mice exposed to a high cholesterol environment during early life.