Pregnancy-Induced Physiologic Adaptation of the Abdominal Aorta Is Associated with Changes in Gene Expression and Genomic Methylation

J Vasc Res. 2018;55(5):319-327. doi: 10.1159/000493682. Epub 2018 Oct 22.

Abstract

Background/aims: Ten-eleven translocation 2 (Tet2), a DNA demethylase enzyme, has been identified as a master epigenetic regulator of vascular smooth muscle cell plasticity. We hypothesized that pregnancy will induce significant adaptive changes in aortic biomechanics that correlate with the Tet family gene expression.

Methods: Abdominal aortas from pregnant and nonpregnant mice were dissected and cannulated. Intraluminal pressure was adjusted using a pressure-servo system while using a video dimension analyzer to measure the lumen diameter. Quantitative polymerase chain reaction and immunoblot was used to analyze the expression of Tet genes. Global genomic methylation was assessed with the luminometric methylation assay.

Results: Compared to the nonpregnant (NP, 706 ± 8 µm) control group, the aortic luminal diameter was significantly increased in both E18.5 (836 ± 14 µm) and PP30 (889 ± 16 µm) mice. Distensibility was reduced in E18.5 (90 ± 4%) mice and returned to NP values (108 ± 2%) in PP30 (108 ± 3%) mice. Tet2 transcription decreased at the beginning of pregnancy and subsequently increased in late gestation, inversely corresponding to changes in global methylation.

Conclusion: Physiologic changes in the aorta were accompanied by changes in gene expression and genomic methylation, suggesting an epigenetic component to maternal vascular remodeling during pregnancy.

Keywords: Aorta; Epigenetics; Pregnancy; Smooth muscle; Tet genes; Vascular smooth muscle.

MeSH terms

  • Adaptation, Physiological
  • Animals
  • Aorta, Abdominal / metabolism*
  • Arterial Pressure
  • DNA Methylation*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Dioxygenases
  • Epigenesis, Genetic*
  • Female
  • Gestational Age
  • Mice
  • Myosin Heavy Chains / genetics
  • Myosin Heavy Chains / metabolism
  • Pregnancy
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Vascular Remodeling / genetics*
  • Vascular Stiffness

Substances

  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • TET1 protein, mouse
  • myosin 11, mouse
  • Dioxygenases
  • Tet2 protein, mouse
  • Myosin Heavy Chains