TY - JOUR
T1 - In utero programming of adult vascular function in transgenic mice lacking low-density lipoprotein receptor
AU - Langenveld, Josje
AU - Lu, Fanxian
AU - Bytautiene, Egle
AU - Anderson, Garland D.
AU - Saade, George R.
AU - Longo, Monica
PY - 2008/8
Y1 - 2008/8
N2 - 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.
AB - 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.
KW - arteriosclerosis
KW - fetal programming
KW - low-density lipoprotein receptor mice
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U2 - 10.1016/j.ajog.2008.01.057
DO - 10.1016/j.ajog.2008.01.057
M3 - Article
C2 - 18359469
AN - SCOPUS:47949094889
SN - 0002-9378
VL - 199
SP - 165.e1-165.e5
JO - American Journal of Obstetrics and Gynecology
JF - American Journal of Obstetrics and Gynecology
IS - 2
ER -