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Published on: February 4, 2015
In utero programming of adult vascular function in transgenic mice lacking low-density lipoprotein receptor
Josje Langenveld1, Fanxian Lu, Egle Bytautiene
1Department of Obstetrics and Gynecology, Máxima Medical Centre, Veldhoven, The Netherlands. josje.langenveld@og.unimaas.nl
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-Ldlr(tm1Her)/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 Ca(2+) 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.
