An increase in elastogenic components in the placental villi of women with chronic venous disease during pregnancy is associated with decreased EGFL7 expression level

Mol Med Rep. 2021 Aug;24(2):556. doi: 10.3892/mmr.2021.12195. Epub 2021 Jun 3.

Abstract

Chronic venous disease (CVD) is the response to a series of hemodynamic changes in the venous system and the onset of this disease is often triggered by pregnancy. Placental tissue is particularly sensitive to the characteristic changes which occurs in venous hypertension. In this regard, changes in the extracellular matrix (ECM), that occur to adapt to this situation, are fundamental to controlling elastogenesis. Therefore, the aim of the present study was to analyze the changes that occur in the mRNA and protein expression level of proteins related to elastogenesis in the placental villi of women diagnosed with CVD, in the third trimester of pregnancy. An observational, analytical and prospective cohort study was conducted, in which the placenta from 62 women with CVD were compared with that in placenta from 52 women without a diagnosis of CVD. Gene and protein expression levels were analyzed using reverse transcription‑quantitative PCR and immunohistochemistry, respectively. The results showed a significant decrease in the gene and protein expression level of EGFL7 in the placental villi of women with CVD. By contrast, significant increases in the gene and protein expression level of ECM‑related proteins, such as tropoelastin, fibulin 4, fibrillin 1 and members of the lysyl oxidase family (LOX and LOXL‑1) were also found in the placental villi of women with CVD. To the best of our knowledge, the results from the present study showed for the first time that CVD during pregnancy was associated with changes in the mRNA and protein expression level in essential components of the EGFL7‑modulated elastogenesis process in placental villi.

Keywords: EGFL7; chronic venous disease; elastogenesis; extracellular matrix; pregnancy.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Amino Acid Oxidoreductases / genetics
  • Amino Acid Oxidoreductases / metabolism
  • Calcium-Binding Proteins / genetics*
  • Calcium-Binding Proteins / metabolism*
  • Chorionic Villi / metabolism*
  • Chorionic Villi / pathology
  • Chronic Disease
  • Cohort Studies
  • EGF Family of Proteins / genetics*
  • EGF Family of Proteins / metabolism*
  • Elastic Tissue / metabolism
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism
  • Female
  • Fibrillin-1 / genetics
  • Fibrillin-1 / metabolism
  • Humans
  • Placenta / metabolism*
  • Placenta / pathology
  • Pregnancy
  • Pregnancy Complications, Cardiovascular / genetics*
  • Pregnancy Complications, Cardiovascular / metabolism*
  • Prospective Studies
  • Protein-Lysine 6-Oxidase / genetics
  • Protein-Lysine 6-Oxidase / metabolism
  • Tropoelastin / genetics
  • Tropoelastin / metabolism
  • Vascular Diseases / metabolism*
  • Young Adult

Substances

  • Calcium-Binding Proteins
  • EFEMP2 protein, human
  • EGF Family of Proteins
  • EGFL7 protein, human
  • Extracellular Matrix Proteins
  • FBN1 protein, human
  • Fibrillin-1
  • Tropoelastin
  • Amino Acid Oxidoreductases
  • LOXL1 protein, human
  • LOX protein, human
  • Protein-Lysine 6-Oxidase

Grants and funding

The study (FIS-PI18/00912) was supported by the Instituto de Salud Carlos III (grant no. Estatal de I + D+I 2013-2016) and co-financed by the European Development Regional Fund ‘A way to achieve Europe’ and B2017/BMD-3804 MITIC-CM (Comunidad de Madrid).