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


Author: Alkemade, F.E. · Gittenberger-Groot, A.C. de · Schiel, A.E. · Munsteren, J.C. van · Hogers, B. · Vliet, L.S.J. van · Poelmann, R.E. · Havekes, L.M. · Dijk, K.W. van · Ruiter, M.C. de
Institution: TNO Kwaliteit van Leven
Source:Arteriosclerosis, Thrombosis, and Vascular Biology, 10, 27, 2228-2235
Identifier: 240233
doi: doi:10.1161/01.ATV.0000282193.31936.fd
Keywords: Health · 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


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.