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

Nima Goharkhay, Esther H. Tamayo, Huaizhi Yin, Gary D.V. Hankins, George R. Saade, Monica Longo

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)273.e1-273.e6
JournalAmerican journal of obstetrics and gynecology
Volume199
Issue number3
DOIs
StatePublished - Sep 2008

Keywords

  • atherosclerosis
  • fetal development
  • fetal programming
  • hypercholesterolemia
  • mouse model

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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