In utero programming of adult vascular function in transgenic mice lacking low-density lipoprotein receptor

Josje Langenveld, Fanxian Lu, Egle Bytautiene, Garland D. Anderson, George R. Saade, Monica Longo

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Objective: The objective of this study was to examine the role of maternal hypercholesterolemia in fetal programming of adult vascular function using transgenic mice lacking the low-density lipoprotein receptor (LDLR). Study Design: Homozygous LDLR knockout mice (B6.129S7-Ldlrtm1Her/J, LDLR-/-KO) and their wild-type controls (C57BL/6J, LDLR+/+WT) were cross-bred to produce 4 litter groups: LDLR-/-KO, maternally derived heterozygous (LDLR±Mat), paternally derived heterozygous (LDLR±Pat) and LDLR+/+WT. Female and male offspring were killed at 10-12 weeks of age, and carotid arteries were used for in vitro experiments. Results: The dose responses to phenylephrine were significantly higher in LDLR-/-KO and LDLR±Mat male offspring. The contractile responses to phenylephrine in female mice were significantly increased only in the LDLR-/-KO offspring. Maximal Ca2+ contraction was higher in LDLR-/-KO male and female offspring. Conclusion: Despite being genomically similar, heterozygous offspring that developed in a hypercholesterolemic maternal environment had abnormal vascular responses later in life compared with those that developed in a normal environment.

Original languageEnglish (US)
Pages (from-to)165.e1-165.e5
JournalAmerican Journal of Obstetrics and Gynecology
Volume199
Issue number2
DOIs
StatePublished - Aug 2008

Keywords

  • arteriosclerosis
  • fetal programming
  • low-density lipoprotein receptor mice

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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