Estrogen Receptors and Chronic Venous Disease

Study Overview
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Brief Summary
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Chronic Venous Disease (CVD) is a very common problem affecting western adult population. To date the pathophysiology of CVD development encloses several theories such as the role of extracellular matrix (ECM) components alterations, the alteration of Matrix Metalloproteinases (MMPs) and other related molecules, the endothelial dysfunction, and several genetic factors but none of these could properly explain its genesis. Estrogen Receptors may be involved in CDV pathogenesis. Endogenous estrogens are important regulators of vascular homeostasis and they act mainly via three different ERs which are expressed in the cardiovascular system: ERα, ERβ, and a G protein-coupled estrogen receptor termed GPER. of this study is to explore the expression of estrogen receptors in vessel wall of varicose veins through the entire clinical spectrum of CVD.

Detailed Description
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Chronic Venous Disease (CVD) is a very common problem affecting western adult population with a prevalence of < 10%, among individuals younger than 30 years for both sex, and with a prevalence of 57% and 77%, in men and women aged ≥ 70 years respectively, and may be frequently associated with other clinical manifestations. The spectrum of CVD ranges from varicose veins to leg edema, and serious dermal clinical manifestations consisting of hyperpigmentation, eczema, lipodermatosclerosis, and venous skin ulceration. To date the pathophysiology of CVD development encloses several theories such as the role of extracellular matrix (ECM) components alterations, the alteration of Matrix Metalloproteinases (MMPs) and other related molecules, the endothelial dysfunction, and several genetic factors but none of these could properly explain its genesis. A recent study (Serra R et al) showed a higher prevalence of CVD among patients with Breast Cancer (BC) respect to general population, especially in those patients that were positive to estrogen receptor (ER) expression. The presence of ERs was investigated in the walls of normal and varicose veins by Mashiah A. et al, previously, and they documented that increased concentrations of estrogen receptors were found in varicose vein segments respect to healthy controls and this was particularly evident in females. Endogenous estrogens are important regulators of vascular homeostasis and they act mainly via three different ERs which are expressed in the cardiovascular system: ERα, ERβ, and a G protein-coupled estrogen receptor termed GPER. Although ERs are also suspected to be involved in the underlying etiology, the exact molecular mechanism responsible for development of CVD as well as the relationship with the wide range of clinical manifestations of CVD remains to be elucidated and the aim of this study is to explore the expression of estrogen receptors in vessel wall of varicose veins collected from patients with varicose veins through the entire clinical spectrum of CVD.

Official Title
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Molecular Analysis of Estrogen Receptors in Patients With Chronic Venous Disease

Conditions
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Estrogen Excess, Varicose Veins

Intervention / Treatment
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* Procedure: Venous Surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with Chronic Venous Disease and varicose veins eligible to receive open venous surgery procedure Exclusion Criteria: Concomitant Peripheral Artery Disease Previous Venous Thromboembolism

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| CVD patients<br>Patients with CVD at various stages (C2-C6 of CEAP classification of CVD) with varicose veins and eligible to receive Open Venous Surgery. | Procedure: Venous Surgery<br>* Patients with Varicose Veins will undergo to venous surgery procedure. Samples obtained from patients undergoing surgical removal of varicose veins will be collected and immediately preserved at -80°. Briefly, the venous tissueswill be excised, homogenized with a motor-driven homogenizer and total RNA will be isolated using the Trizol reagent (Invitrogen, Milan, Italy), according to the manufacturer's instructions. The expression of ERα, ERβ and GPER will be quantified by real-time PCR using the Step OneTM sequence detection system (Applied Biosystems Inc., Milan, Italy), following the manufacturer's instructions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| expression of ERα, ERβ and GPER | The expression of ERα, ERβ and GPER will be quantified by real-time PCR using the Step OneTM sequence detection system (Applied Biosystems Inc., Milan, Italy), following the manufacturer's instructions | At month 9th | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Venous Disease, Estrogen receptors, GPER