W. Palinski et al., Maternal hypercholesterolemia and treatment during pregnancy influence thelong-term progression of atherosclerosis in offspring of rabbits, CIRCUL RES, 89(11), 2001, pp. 991-996
Maternal hypercholesterolemia during pregnancy is associated with enhanced
fatty streak formation in human fetuses and faster progression of atheroscl
erosis during childhood even under normocholesterolemic conditions. A causa
l role of maternal hypercholesterolemia in lesion formation during fetal de
velopment has previously been established in rabbits. The same experimental
model is now used to establish that maternal hypercholesterolemia or ensui
ng pathogenic events in fetal arteries enhance atherogenesis later in life.
Five groups of rabbit mothers were fed chow, cholesterol-enriched chow, or
cholesterol-enriched chow plus 1000 lU vitamin E, 3% cholestyramine, or bo
th during pregnancy. Offspring of all groups (n = 136) were fed a mildly hy
percholesterolemic diet for up to a year and had similar cholesterol levels
. Aortic lesion sizes and lipid peroxidation products in plasma and lesions
in offspring were determined at birth, 6 months, or 12 months. Lesion prog
ression in offspring of hypercholesterolemic mothers was greater than in al
l other groups. At each time point, offspring of hypercholesterolemic mothe
rs had 1.5- to 3-fold larger lesions than offspring of normocholesterolemic
mothers (P<0.01), with the greatest absolute differences at 12 months. Mat
ernal treatment reduced lesions by 19% to 53%, compared with offspring of u
ntreated hypercholesterolemic mothers (P<0.01), with the greatest effect in
the vitamin E groups. At 12 months, lesions in offspring of all vitamin E
and cholestyramine-treated mothers were similar to those of normocholestero
lemic mothers. Lipid peroxidation end-products in lesions and plasma showed
analogous differences between groups as lesions (P<0.01). Thus, pathogenic
programming in utero increases the susceptibility to atherogenic risk fact
ors later in life and maternal intervention with cholesterol-lowering drugs
or antioxidants reduce postnatal lipid peroxidation and atherosclerosis in
their offspring.