The fetal origins of atherosclerosis: maternal hypercholesterolemia, and cholesterol-lowering or antioxidant treatment during pregnancy influence in utero programming and postnatal susceptibility to atherogenesis.
نویسندگان
چکیده
It has long been postulated that pathogenic events during fetal development influence atherosclerosis-related diseases later in life, but the mechanisms involved are unknown. This review focuses on the evidence indicating that maternal hypercholesterolemia during pregnancy is responsible for one cascade of pathogenic events. Maternal hypercholesterolemia is associated with greatly increased fatty streak formation in human fetal arteries and accelerated progression of atherosclerosis during childhood. Recent experiments in genetically more homogeneous rabbits established that temporary diet-induced maternal hypercholesterolemia is sufficient to enhance fetal lesion formation. More important, maternal hypercholesterolemia or ensuing pathogenic events in the fetus increase postnatal atherogenesis in response to hypercholesterolemia. Maternal treatment with cholesterol-lowering agents or antioxidants greatly reduces fetal and postnatal atherogenesis, indicating a pathogenic role of lipid peroxidation and a potential involvement of oxidation-sensitive signaling pathways. Experiments in a murine model showed that differences in arterial gene expression between offspring of normo- and hypercholesterolemic mothers persist long after birth, supporting the assumption that fetal lesion formation is associated with genetic programming, which may in turn affect postnatal atherogenesis. A better understanding of pathogenic programming events in utero may lead to the identification of genes determining the susceptibility to atherosclerosis and define novel preventive approaches.
منابع مشابه
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ورودعنوان ژورنال:
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology
دوره 16 11 شماره
صفحات -
تاریخ انتشار 2002