Gene Expression in Chronic Venous Leg Ulcers

Overview

Chronic Venous Disease (CVD) is a widespread clinical condition widely spread in the western countries that may negatively impact the quality of life (QoL) of affected patients. Chronic venous leg ulcers (CVLUs) are the most severe form of CVD, and several genetic and molecular alterations have been studied in order to understand the progression of CVD towards CLVUs. Chronic inflammation is a key element in CVLUs onset, and recently T helper 17 (Th-17) cells, a subtype of pro-inflammatory T helper (CD4+) cells defined by the production of a cytokine signature of which IL-17 represents the progenitor, seem to be related to several chronic disease. The aim of this study is to evaluate Th17- Gene Expression profile in patients with CVD and CVLUs.

Chronic Venous Disease (CVD) is a widespread clinical condition widely spread in the western countries, with a prevalence ranging from 10% in adults younger than 30 years of age to nearly 80% for individuals \>70 years of age. CVD clinical manifestations vary from mild clinical signs, including varicose veins, to more advanced and severe signs such as chronic venous leg ulcers (CVLUs) which significantly impact the quality of life (QoL) of affected patients. Several genetic and molecular alterations have been studied so far to understand the onset, progression, and complications of CVD, including Chronic Venous Insufficiency (CVI) states in which CVLUs may develop. The appearance of CVLUs is generally preceded by skin changes of the lower limbs such as lipodermatosclerosis, that is a chronic inflammatory condition due to CVI, characterised by an inflammatory skin condition. This pathological event leads to subcutaneous fibrosis and hardening of the affected skin, resulting in tissue hypoxia essential for venous ulceration.Gene expression profile studies, present in the current literature, allow us to hypothesize several mechanisms underlying the development of CVLU, highlighting a wide variety of genetic-molecular interconnections. Nevertheless, none to date is able to provide a genetic and cellular model linking the pathogenetic events that lead to the onset of CVLU or the progression of these lesions.T helper 17 (Th-17) cells are a subtype of pro-inflammatory T helper (CD4+) cells defined by the production of a cytokine signature of which IL-17 represents the progenitor. The development and differentiation and expansion of Th-17 depends on differentiation factors (TGF- β ), growth factors (IL-23/IL23R) and several transcription factors (ROR-γt, STAT3 ). Interestingly, the Th-17 axis has been implicated in several autoimmune diseases including rheumatoid arthritis, multiple sclerosis, ulcerative colitis, Crohn's disease, psoriasis, and autoimmune encephalitis among others. In addition, an increasingly strong role of the Th-17 axis in tumor drug resistance and in the progression and radicalization of HIV infection is recently emerging. Our study aims at evaluation Th17- Gene Expression profile in patients with CVD and CVLUs.