Characterization of a murine model of fetal programming of atherosclerosis.

Abstract

The objective of the study was to investigate the effect of fetal programming on the development of atherosclerosis in the offspring in a mouse model. Male and female mice of the wild type and the knockout for the apoprotein E (apoE) gene were cross-bred to obtain all 4 possible genetic offspring types. The offspring were kept on regular chow and killed at 8 months of age. Levels of total cholesterol and triglycerides were determined. The aortic arch was examined for the presence and severity of atherosclerosis. Kidney and liver sections were analyzed for pathologic changes. We found increased total cholesterol levels and incidence of atherosclerosis in offspring born to hypercholesterolemic mothers as compared with genomically similar animals born to wild-type mothers. These animals also showed kidney and liver lesions consistent with chronic hypercholesterolemia. There is a strong effect of fetal programming on the development of atherosclerosis in the apoE mouse model.