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

作者:	Josje Langenveld, Fanxian Lu, Egle Bytautiene, Garland D Anderson, George R Saade, Monica Longo
语言:	ENG.
日期:	24-3-2008
学报:	American journal of obstetrics and gynecology (1097-6868)
发行:	Am J Obstet Gynecol. 21 Mar 2008
摘要:	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.
版权:	American journal of obstetrics and gynecology Department of Obstetrics and Gynecology, Máxima Medical Centre, Veldhoven, The Netherlands.
全文:	American journal of obstetrics and gynecology (DOI) Elsevier Science - HTML (需要捐款) Swets Information Services - HTML (需要捐款)