Newborns of Mothers with Venous Disease during Pregnancy Show Increased Levels of Lipid Peroxidation and Markers of Oxidative Stress and Hypoxia in the Umbilical Cord

Abstract

Chronic venous disease (CVD) encompasses a set of disorders of the venous system that have a high prevalence in Western societies and are associated with significant sociohealth costs. Pregnancy is a period in which different hormonal and haemodynamic changes occur that lead to significant changes in the cardiovascular system, increasing the risk of developing venous problems, especially during the third trimester of gestation. In turn, CVD involves a series of local and systemic alterations that can have negative repercussions in pregnancy. In this context, the role of oxidative stress in the pathophysiology of this condition has been shown to significantly affect other vascular structures during pregnancy, such as the placenta. However, the effects of oxidative stress on the umbilical cord in women with CVD have not yet been fully elucidated. Thus, the objective of this study was to analyse the gene and protein expression of the enzymes NOX-1, NOX-2 and iNOS, which are involved in the production of reactive oxygen and nitrogen species, respectively. Similarly, the presence of hypoxia-inducible factor 1-alpha (HIF-1α) in the umbilical cord in women with CVD was compared to that of pregnant control women, and the levels of the lipid peroxidation marker malonyldialdehyde (MDA) in cord tissue and blood was also analysed. Our results support a significant increase in the enzymes NOX-1, NOX-2 and iNOS and HIF-1α and MDA in the umbilical cord tissue and blood of women with CVD. For the first time, our work demonstrates an increase in oxidative stress and cellular damage in the umbilical cords of pregnant women who develop this condition, deepening the understanding of the consequences of CVD during pregnancy.

The Pivotal Role of the Placenta in Normal and Pathological Pregnancies: A Focus on Preeclampsia, Fetal Growth Restriction, and Maternal Chronic Venous Disease

“…The hypoxic environment observed in these placentas was related to an increased number of villi together with enhanced apoptosis and syncytial knot detection in comparison with the women in the control group. Moreover, similar results were also found in the umbilical cord of these women [265], therefore evidencing the association between CVeD with hypoxia and oxidative stress in the maternofetal structures during pregnancy. The various alterations related to CVeD promote an abnormal environment in the placental tissue, leading to the development of different adaptative responses.…”

Chronic Venous Disease during Pregnancy Causes a Systematic Increase in Maternal and Fetal Proinflammatory Markers

“…In fact, it has been demonstrated that CVD itself causes noteworthy changes in cytokine production by the immune cells, hence inducing proinflammatory profiling [ 32 ]. CVD has also been associated with placental, umbilical cord, and systemic oxidative stress [ 14 , 33 ]. Moreover, an altered local detection of some cytokines has also been observed in the placenta of women with CVD, which is closely related to abnormal cell and molecular behavior [ 34 , 35 , 36 ].…”

Understanding Chronic Venous Disease: A Critical Overview of Its Pathophysiology and Medical Management

“…The reasons why women are more likely to suffer from CVD, reside on different hormonal and physiological factors that make them more sensitive to develop this condition [ 32 ]. In this group, pregnant women (PW) are more prone to develop this condition, with approximately 40% of them suffering from CVD [ 33 ]. In addition, the number of pregnancies might also be a variable of note to acquire this condition.…”

“…According to Shadrina et al, PPP3R1 , EBF1 , GATA2 and NFATC2 were genes associated to immune response or inflammation in vascular remodeling, a noted part related to VVs [ 239 ]. PPP3R1 (protein phosphatase 3 regulatory subunit B, alpha) associated variants, rs2861819 and rs2241173, have been studied as genetic determinants for CVD development, being involved in vascular integrity [ 33 ]. EBF1 (early b cell factor transcription factor 1) has a role in cell adhesion and migration during early B lymphopoiesis, being crucial for managing B cell immunity, and provides susceptibility to VV by its variant rs11135046 [ 245 , 246 ].…”