Intrauterine Exposure to Maternal Atherosclerotic Risk Factors Increases.pptVIP

Intrauterine Exposure to Maternal Atherosclerotic Risk Factors Increases the Susceptibility to Atherosclerosis in Adult LifeFanneke E. Alkemade, Marco C. DeRuiter, et al. Arterioscler Thromb Vasc Biol. 2007;27:2228-2235. Introduction Fatty Streak Formation Occurs in Fetal Aortas and is Enhanced byMaternal Hypercholesterolemia,1997 Napoli. J Clin. Invest. 100, 2680–2690 Fate of Early Lesions in ChildrenFELIC study,1999 Napoli. Lancet 354, 1234–1241 Raised cholesterol intake of pregnant LDL-/- mice accelerated the progression of spontaneous atherosclerotic lesions in the LDL-/- progeny. hypothesis The offspring without a genetic predisposition for spontaneous atherosclerosis, which had been exposed in utero to maternal atherosclerotic risk factors, would show increased susceptibility to atherosclerosis development in adult life compared with offspring of wild-type mothers. Methods and Results Maternal plasma cholesterol and triglyceride levels Offspring plasma cholesterol and triglyceride levels Effects of in utero exposure of apoE+/- fetuses to maternal atherosclerotic risk factors on endothelial cells of the carotidarteries Effects of a constrictive collar four weeks after placement around the left common carotid artery Morphology of adult carotid arteries Morphometric analysis of the effects of collar placement Oil Red O staining Neointima composition conclusion Maternal hypercholesterolemia resulted in a significant plasma cholesterol elevation in apoE+/- mice at E17.5 Significant increase in loss of endothelial cell volume was observed in the carotid arteries of fetuses of apoE -/- mice Collar placement resulted in severe neointima formation proximal to the collar in apoE +/- mice of apoE -/- mothers Development programming Histone methylation patterning after intrauterine exposure to maternal apoE-deficiency and postnatal normal versus high cholesterol diet Quantitative analysis of histone methylation pattern