Increased Angiogenesis and Lymphangiogenesis in the Placental Villi of Women with Chronic Venous Disease during Pregnancy

Int J Mol Sci. 2020 Apr 3;21(7):2487. doi: 10.3390/ijms21072487.

Abstract

Pregnancy is a period in a woman's life associated with an increased risk of developing lower extremity chronic venous disease (CVD). Pregnancy-associated CVD is associated with changes in placental villi. We investigated angiogenesis and lymphangiogenesis in the placental villi of women with CVD during pregnancy compared with healthy controls with no history of CVD (HC). An observational, analytical, and prospective cohort study was conducted on 114 women in their third trimester of pregnancy (32 weeks). Sixty-two participants were clinically diagnosed with CVD. In parallel, 52 controls with no history of CVD (HC) were studied. Gene and protein expression of CD31, podoplanin (D2-40), Flt-1, and placental growth factor (PIGF) was analysed by real-time polymerase chain reaction (RT-qPCR) and immunohistochemistry. CD31 and D2-40 gene expression was significantly greater in the placental villi of women with CVD, as were the numbers of vessels positive for CD31 and D2-40. Significantly higher gene and protein expression of Flt-1 and PIGF was observed in the placental villi of women with CVD. Histological analysis showed more placental villi with periodic acid of Schiff (PAS)-positive material in women with CVD. Our results show a connection between pregnancy-associated CVD and leading to higher proangiogenic and lymphangiogenic activity in placental villi.

Keywords: CD31; PIGF; chronic venous disease; podoplanin (D2-40), Flt-1; pregnancy.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Biomarkers / metabolism
  • Case-Control Studies
  • Chorionic Villi / metabolism*
  • Female
  • Gestational Age
  • Humans
  • Maternal Age
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / metabolism
  • Placenta Growth Factor / genetics*
  • Placenta Growth Factor / metabolism
  • Platelet Endothelial Cell Adhesion Molecule-1 / genetics*
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Pregnancy
  • Pregnancy Complications, Cardiovascular
  • Prospective Studies
  • Up-Regulation*
  • Varicose Veins / genetics*
  • Varicose Veins / metabolism
  • Vascular Endothelial Growth Factor Receptor-1 / genetics*
  • Vascular Endothelial Growth Factor Receptor-1 / metabolism
  • Young Adult

Substances

  • Biomarkers
  • Membrane Glycoproteins
  • PDPN protein, human
  • PECAM1 protein, human
  • PGF protein, human
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Placenta Growth Factor
  • FLT1 protein, human
  • Vascular Endothelial Growth Factor Receptor-1