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.
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 miceborn 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.
Authors: W Palinski; F P D'Armiento; J L Witztum; F de Nigris; F Casanada; M Condorelli; M Silvestre; C Napoli Journal: Circ Res Date: 2001-11-23 Impact factor: 17.367
Authors: C Napoli; F P D'Armiento; F P Mancini; A Postiglione; J L Witztum; G Palumbo; W Palinski Journal: J Clin Invest Date: 1997-12-01 Impact factor: 14.808
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