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. © 2008 Mosby, Inc. All rights reserved.
Langenveld, J., Lu, F., Bytautiene, E., Anderson, G. D., Saade, G. R., & Longo, M. (2008). In utero programming of adult vascular function in transgenic mice lacking low-density lipoprotein receptor. American Journal of Obstetrics and Gynecology, 199(2), 165.e1-165.e5. https://doi.org/10.1016/j.ajog.2008.01.057