Dataset Information


Transcription profiling of mouse offspring of crosses between hypercholesterolemic and normocholesterolemic parents LUMC-HKG-ApoE-Atherosclerosis

ABSTRACT: Enhanced prenatal fatty streak formation in human fetuses has been associated with maternal hypercholesterolemia. However, the possible roles of maternal genetic background and in utero environment on development of atherosclerosis in adult life have not been unraveled. We generated genetically identical heterozygous apoE-deficient mice offspring with a different maternal background to study the intrauterine effect of maternal genotype and associated hypercholesterolemia on the developing vascular system. As read out for increased atherosclerosis development in adult life, a constrictive collar was placed around the carotid artery to induce lesion formation. A significant increase in endothelial cell activation and damage was detected in the carotid arteries of heterozygous apoE-deficient fetuses with apoE-deficient mothers compared with offspring from wild type mothers, but no fatty streak formation was observed. Postnatally, all carotid arteries revealed normal morphology. In adult offspring with maternal apoE-deficiency, the constrictive collar resulted in severe lesion (9/10) development compared with no to only minor lesions (2/10) in offspring of wild type mothers. Microarray analysis showed no effect of maternal apoE-deficiency on gene expression in adult offspring. We conclude that maternal apoE-deficiency not only affects fetal arteries, but also increases the susceptibility for development of collar-induced atherosclerosis in adult life. Experiment Overall Design: Crossing of hypercholesterolemic female with normocholesterolemic male and vice versa, determination of susceptabilioty to atherosclerosis in offspring

INSTRUMENT(S): 418 [Affymetrix]

ORGANISM(S): Mus musculus  

SUBMITTER: Anja Schiel  

PROVIDER: E-GEOD-6134 | ArrayExpress | 2008-06-14



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Intrauterine exposure to maternal atherosclerotic risk factors increases the susceptibility to atherosclerosis in adult life.

Alkemade Fanneke E FE   Gittenberger-de Groot Adriana C AC   Schiel Anja E AE   VanMunsteren J Conny JC   Hogers Bianca B   van Vliet Leontien S J LS   Poelmann Robert E RE   Havekes Louis M LM   Willems van Dijk Ko K   DeRuiter Marco C MC  

Arteriosclerosis, thrombosis, and vascular biology 20070726 10

OBJECTIVE: Maternal hypercholesterolemia is associated with a higher incidence and faster progression of atherosclerotic lesions in neonatal offspring. We aimed to determine whether an in utero environment exposing a fetus to maternal hypercholesterolemia and associated risk factors can prime the murine vessel wall to accelerated development of cardiovascular disease in adult life. METHODS AND RESULTS: To investigate the epigenetic effect in utero, we generated genetically identical heterozygous  ...[more]

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