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 Saade, Monica Longo

Research output: Contribution to journalArticle

5 Citations (Scopus)

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)
JournalAmerican Journal of Obstetrics and Gynecology
Volume199
Issue number2
DOIs
StatePublished - Aug 2008

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LDL Receptors
Transgenic Mice
Blood Vessels
Phenylephrine
Mothers
Fetal Development
Hypercholesterolemia
Carotid Arteries
Knockout Mice

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)
  • Obstetrics and Gynecology

Cite this

In utero programming of adult vascular function in transgenic mice lacking low-density lipoprotein receptor. / Langenveld, Josje; Lu, Fanxian; Bytautiene, Egle; Anderson, Garland D.; Saade, George; Longo, Monica.

In: American Journal of Obstetrics and Gynecology, Vol. 199, No. 2, 08.2008.

Research output: Contribution to journalArticle

Langenveld, Josje ; Lu, Fanxian ; Bytautiene, Egle ; Anderson, Garland D. ; Saade, George ; Longo, Monica. / In utero programming of adult vascular function in transgenic mice lacking low-density lipoprotein receptor. In: American Journal of Obstetrics and Gynecology. 2008 ; Vol. 199, No. 2.
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