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


METHODS
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.


CONCLUSIONS
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.
Langenveld
Josje
J
Department of Obstetrics and Gynecology, Máxima Medical Centre, Veldhoven, The Netherlands. josje.langenveld@og.unimaas.nl
Lu
Fanxian
F
Bytautiene
Egle
E
Anderson
Garland D
GD
Saade
George R
GR
Longo
Monica
M
D000818:Animals; D001808:Blood Vessels / Q000196:embryology*; D002339:Carotid Arteries / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006937:Hypercholesterolemia / Q000196:embryology* / Q000503:physiopathology; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010656:Phenylephrine / Q000494:pharmacology; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000503:physiopathology*; D011973:Receptors, LDL / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D011973:Receptors, LDL; D014662:Vasoconstrictor Agents; D010656:Phenylephrine