Several studies have suggested a strong association between total maternal cholesterol and low-density lipoprotein cholesterol (LDLC) levels during pregnancy and the risk of atherosclerotic disease in the offspring. This study aims to investigate whether epigenetic signatures are a characteristic of early fetal atherogenesis associated with hypercholesterolemia.

This autopsy study included a total of 78 human fetal aorta autopsy samples. The researchers determined maternal cholesterol levels, high-density lipoprotein, LDLC, triglycerides, glucose levels, and body mass index (BMI). The primary outcomes of the study were the results of DNA methylation and messenger RNA levels of genes involved in cholesterol metabolism.

Multivariate analysis suggested that maternal cholesterol level was significantly associated with fetal aortic lesion variance (61%). The effect was independently associated with the levels of HDLC, triglycerides, glucose, and BMI. In addition, LDLC and maternal cholesterol levels were linearly associated with the methylation of SREBP2 in fetal. In univariate analysis, they were inversely related to SREBP2 messenger RNA levels in fetal aortas. The findings also suggested epivariations of genes controlling cholesterol metabolism in cholesterol-treated human aortic endothelial cells.

The research concluded that maternal cholesterol levels during pregnancy were associated with fetal aortic lesions and had an epigenetic response of fetal aortic SREBP2.