DNA Methylation Profile of the SREBF2 Gene in Human Fetal Aortas

J Vasc Res. 2022;59(1):61-68. doi: 10.1159/000518513. Epub 2021 Sep 14.

Abstract

Increasing evidence suggests that maternal cholesterol represents an important risk factor for atherosclerotic disease in offspring already during pregnancy, although the underlying mechanisms have not yet been elucidated. Eighteen human fetal aorta samples were collected from the spontaneously aborted fetuses of normal cholesterolemic and hypercholesterolemic mothers. Maternal total cholesterol levels were assessed during hospitalization. DNA methylation profiling of the whole SREBF2 gene CpG island was performed (p value <0.05). The Mann-Whitney U test was used for comparison between the 2 groups. For the first time, our study revealed that in fetal aortas obtained from hypercholesterolemic mothers, the SREBF2 gene shows 4 significant differentially hypermethylated sites in the 5'UTR-CpG island. This finding indicates that more effective long-term primary cardiovascular prevention programs need to be designed for the offspring of mothers with hypercholesterolemia. Further studies should be conducted to clarify the epigenetic mechanisms underlying the association between early atherogenesis and maternal hypercholesterolemia during pregnancy.

Keywords: Aortas; Atherosclerosis; Cholesterol; Dyslipidemia; Fetus; SREBF2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aorta / embryology
  • Aorta / metabolism*
  • Biomarkers / blood
  • Case-Control Studies
  • Cholesterol / blood
  • DNA Methylation*
  • Epigenesis, Genetic*
  • Epigenome
  • Female
  • Gene Expression Regulation, Developmental
  • Gene Regulatory Networks
  • Gestational Age
  • Humans
  • Hypercholesterolemia / blood
  • Hypercholesterolemia / genetics*
  • Pregnancy
  • Pregnancy Complications / blood
  • Pregnancy Complications / genetics*
  • Protein Interaction Maps
  • Sterol Regulatory Element Binding Protein 2 / genetics*

Substances

  • Biomarkers
  • SREBF2 protein, human
  • Sterol Regulatory Element Binding Protein 2
  • Cholesterol