Chronic Venous Disease in Pregnant Women Causes an Increase in ILK in the Placental Villi Associated with a Decrease in E-Cadherin.

Miguel A Ortega,Coral Bravo,Iris Cruza,Miguel Angel Alvarez-Mon,César Menor-Salván,Oscar Fraile-Martinez,Cielo García-Montero,Juan De Leon-Luis,Chen Chaowen,Miguel A Saez,Angel Asúnsolo-Del-Barco,Yuliia Fatych,Claude Pereda-Cerquella,Luis G Guijarro,Natalio Garcia-Honduvilla,Melchor Alvarez-Mon,Julia Buján

doi:10.3390/jpm12020277

Abstract

Chronic venous disease (CVD) is a multifactorial vascular disorder frequently manifested in lower limbs in the form of varicose veins (VVs). Women are a vulnerable population for suffering from CVD, especially during pregnancy, when a plethora of changes occur in their cardiovascular system. Previous studies have indicated a worrisome association between CVD in pregnancy with the placental structure and function. Findings include an altered cellular behavior and extracellular matrix (ECM) composition. Integrin-linked kinase (ILK) is a critical molecule involved in multiple physiological and pathological conditions, and together with cadherins, is essential to mediate cell to ECM and cell to cell interplay, respectively. Thus, the aim of this study was to evaluate the implication of ILK and a set of cadherins (e-cadherin, cadherin-6 and cadherin-17) in placentas of women with CVD in order to unravel the possible pathophysiological role of these components. Gene expression (RT-qPCR) and protein expression (immunohistochemistry) studies were performed. Our results show a significant increase in the gene and protein expression of ILK, cadherin-6 and cadherin-17 and a decrease of e-cadherin in the placenta of women with CVD. Overall, this work shows that an abnormal expression of ILK, e-cadherin, cadherin-6 and cadherin-17 may be implicated in the pathological changes occurring in the placental tissue. Further studies should be conducted to determine the possible associations of these changes with maternal and fetal well-being.

Highlights

Chronic Venous Disease (CVD) is a vascular disorder frequently manifested by the appearance of varicose veins (VVs), generally in the lower limbs [1]
Our results have shown a significant increase in Integrin-linked kinase (ILK) gene expression in the placental villi of women with Chronic venous disease (CVD) during pregnancy compared to healthy controls (HC), *** p < 0.001 [CVD = 35.027
Of 12expression in the placental villi of women with CVD during pregnancy compared to HC, *** p < 0.001

Summary

Introduction

Chronic Venous Disease (CVD) is a vascular disorder frequently manifested by the appearance of varicose veins (VVs), generally in the lower limbs [1]. These alterations include notable hemodynamic modifications, variations in the oxygen transport and a profound vascular remodeling [3,4]. This may lead to the development of CVD, which is associated with the detection of different local and systemic markers of damage that could entail negative consequences for the maternofetal well-being [5]. Different studies indicate that approximately 1 in 3 women during pregnancy may suffer from VVs [6,7] and these data could increase to 50–70% when considering additional manifestations of CVD [8].

Objectives

Methods

Results

Discussion

Conclusion