To determine the effects of hypercholesterolemia in pregnant mice on the susceptibility to atherosclerosis in adult life through a new animal modeling approach.

Male offspring from apoE–/– mice fed with regular (R) or high (H) cholesterol chow during pregnancy were randomly subjected to regular (Groups R–R and H–R, n = 10) or high cholesterol diet (Groups R–H and H–H, n = 10) for 14 weeks. Plasma lipid profiles were determined in all rats. The abdominal aorta was examined for the severity of atherosclerotic lesions in offspring.

Lipids significantly increased while high-density lipoprotein-cholesterol/low-density lipoprotein-cholesterol decreased in mothers fed high cholesterol chow after delivery compared with before pregnancy (p < 0.01). Groups R–H and H–R indicated dyslipidemia and significant atherosclerotic lesions. Group H–H demonstrated the highest lipids, lowest high-density lipoprotein-cholesterol/low-density lipoprotein-cholesterol, highest incidence (90%), plaque area to luminal area ratio (0.78 ± 0.02) and intima to media ratio (1.57 ± 0.05).

Hypercholesterolemia in pregnant mice may increase susceptibility to atherosclerosis in their adult offspring.