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

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-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.

• Authors: Josje Langenveld, Fanxian Lu, Egle Bytautiene, Garland D Anderson, George R Saade, Monica Longo
• Journal: American journal of obstetrics and gynecology (Am J Obstet Gynecol) Vol. 199 Issue 2 Pg. 165.e1-5 (Aug 2008) ISSN: 1097-6868 [Electronic] United States
• PMID: 18359469 (Publication Type: Journal Article)

Chemical References

• Receptors, LDL
• Vasoconstrictor Agents
• Phenylephrine

Topics

• Animals
• Blood Vessels (embryology)
• Carotid Arteries (physiology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Female
• Hypercholesterolemia (embryology, physiopathology)
• In Vitro Techniques
• Mice
• Mice, Knockout
• Mice, Transgenic
• Phenylephrine (pharmacology)
• Pregnancy
• Pregnancy Complications, Cardiovascular (physiopathology)
• Receptors, LDL (physiology)
• Vasoconstrictor Agents (pharmacology)