Irregular Expression of Cellular Stress Response Markers in the Placenta of Women with Chronic Venous Disease

Pregnancy comprises a period in a woman’s life in which the circulatory system is subjected to hemodynamical and biochemical changes. During this period, while restructuring blood vessels and exchanging maternal-fetal products there is an increased risk of developing chronic venous disease (CVD), wh...

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Bibliographic Details
Authors: García Montero, Cielo, Fraile Martínez, Oscar, Rodriguez Martín, Sonia, Funes Moñux, Rosa M., Saz, Jose V., Bravo Arribas, Coral, León Luis, Juan Antonio, Ruiz Minaya, Maria, Pekarek, Leonel, Saez, Miguel A., García Lledó, Alberto, Álvarez Mon, Melchor, Bujan, Julia, García Honduvilla, Natalio, Ortega, Miguel A.
Format: article
Publication Date:2022
Country:España
Institution:Universidad Complutense de Madrid (UCM)
Repository:Docta Complutense
Language:English
OAI Identifier:oai:docta.ucm.es:20.500.14352/72300
Online Access:https://hdl.handle.net/20.500.14352/72300
Access Level:Open access
Keyword:618.2
Chronic venous disease
Placenta
Oxidative stress
NRF2
KEAP1
CUL3
GSK-3β
Medicina
Ginecología y obstetricia
Sistema cardiovascular
32 Ciencias Médicas
3201.08 Ginecología
2411.03 Fisiología Cardiovascular
Description
Summary:Pregnancy comprises a period in a woman’s life in which the circulatory system is subjected to hemodynamical and biochemical changes. During this period, while restructuring blood vessels and exchanging maternal-fetal products there is an increased risk of developing chronic venous disease (CVD), which may have an echo in life after childbirth for both mother and child. Previously, we investigated that pregnancy-associated CVD involves changes in placental architecture at angiogenesis, lymphangiogenesis and villi morphology compared with healthy controls (HC) with no history of CVD. We aimed to more deeply investigate the oxidative stress response in placenta from women with CVD versus HC through several markers (NRF2, KEAP1, CUL3, GSK-3β). An observational, analytical, and prospective cohort study was conducted on 114 women in their third trimester of pregnancy (32 weeks). A total of 62 participants were clinically diagnosed with CVD. In parallel, 52 controls with no history of CVD (HC) were studied. Gene and protein expressions of NRF2, KEAP1, CUL3, GSK-3β were analyzed by real-time polymerase chain reaction (RT-qPCR) and immunohistochemistry. Nrf2 gene and protein expression was significantly greater in placental villi of women with CVD, while Keap1, CUL-3 and GSK-3β gene and protein expressions were significantly lower. Our results defined an aberrant gene and protein expression of Nrf2 and some of their main regulators Keap1, CUL-3 and GSK-3 β in the placenta of women with CVD, which could be an indicator of an oxidative environment observed in this tissue.

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