Title
Intrauterine exposure to maternal atherosclerotic risk factors increases the susceptibility to atherosclerosis in adult life
Author
TNO Kwaliteit van Leven
Alkemade, F.E.
de Gittenberger-Groot, A.C.
Schiel, A.E.
van Munsteren, J.C.
Hogers, B.
van Vliet, L.S.J.
Poelmann, R.E.
Havekes, L.M.
van Dijk, K.W.
de Ruiter, M.C.
Publication year
2007
Abstract
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 apolipoprotein E-deficient progeny from mothers with a wild-type or apolipoprotein E-deficient background. A significant increase in loss of endothelial cell volume was observed in the carotid arteries of fetuses of apolipoprotein E-deficient mothers, but fatty streak formation was absent. Spontaneous atherosclerosis development was absent in the aorta and carotid arteries in adult life. We unilaterally placed a constrictive collar around the carotid artery to induce lesion formation. In offspring from apolipoprotein E-deficient mothers, collar placement resulted in severe neointima formation in 9 of 10 mice analyzed compared with only minor lesion volume (2 of 10) in the progeny of wild-type mothers. CONCLUSIONS - We conclude that the susceptibility to neointima formation of morphologically normal adult arteries is already imprinted during prenatal development and manifests itself in the presence of additional atherogenic risk factors in adult life. Future research will concentrate on the mechanisms involved in this priming process, as well as on prevention strategies. © 2007 American Heart Association, Inc.
Subject
Biomedical Research
Atherosclerosis
Carotid arteries
Hypercholesterolemia
Pregnancy
Risk factors
apolipoprotein E
cholesterol
triacylglycerol
atherosclerosis
cardiovascular risk
carotid artery
cell volume
comparative study
controlled study
disease predisposition
endothelium cell
epigenetics
female
heterozygosity
hypercholesterolemia
hyperlipoproteinemia type 3
intima
maternal disease
mother
mouse
nonhuman
prenatal development
prenatal exposure
progeny
risk factor
statistical significance
wild type
animal
blood
C57BL mouse
carotid artery injury
cell size
disease course
disease model
fetus blood
genetic epigenesis
genetics
genome imprinting
hospitalization
human
magnetic resonance angiography
metabolism
mouse mutant
pathology
pregnancy
transgenic mouse
Animals
Apolipoproteins E
Atherosclerosis
Carotid Arteries
Carotid Artery Injuries
Cell Size
Cholesterol
Disease Models, Animal
Disease Progression
Endothelial Cells
Epigenesis, Genetic
Female
Fetal Blood
Genomic Imprinting
Humans
Hypercholesterolemia
Magnetic Resonance Angiography
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Pregnancy
Prenatal Exposure Delayed Effects
Risk Factors
Severity of Illness Index
Triglycerides
Tunica Intima
To reference this document use:
http://resolver.tudelft.nl/uuid:42195914-8e41-4a5d-a5e2-7c026fbabeeb
DOI
https://doi.org/10.1161/01.atv.0000282193.31936.fd
TNO identifier
240233
ISSN
1079-5642
Source
Arteriosclerosis, Thrombosis, and Vascular Biology, 27 (27), 2228-2235
Document type
article