A Novel View to Varicose Veins Pathogenesis: Proteomic Analysis

Abstract

Introduction - The advent of proteomics techniques allows large-scale studies of gene expression at protein level. Although morphological and anatomical studies indicate that venous wall weakening and subendothelial fibrosis characterize varicose veins, the pathogenesis of varicose veins remains poorly understood. The aim this study is to obtain protein expression profiles in patients with varicose veins. Finally, the identification of possible biomarkers may open possibilities for pharmacological inhibition of disease progression. Methods - Varicose saphenous veins removed during phlebectomy and normal saphenous veins obtained during vascular surgery were collected for proteomics analysis. The same layers of venous wall from varicose and non-varicose veins were incubated, and the proteins released were analyzed by ion mobility spectrometry (IMS-MS) with Synapt G2.All differentially expressed proteins and their pathways, coexpression and physical interactions were analyzed in GeneMANIA and AmiGO databases. Results - Proteomic analysis of the human vein revealed totally 1387 proteins. 200 proteins demonstrated significant differences in their quantity (more than 1.5 fold) between the two types of venous tissue (p<0.05). Among the most differentially expressed proteins 10 were found significantly decreased in the varicose vein tissue, and only two- increased. CXXC-type zinc finger protein was more permanent (38- fold down regulated). This protein is known as receptor for vascular endothelial growth factor. Most prominent proteins were proved with Western Blotting analysis. Conclusion - This study provides novel insights into the biochemical mechanisms of this disease and a basis for further studies. Our proteomics discovery approach suggests that extracellular matrix degradation play a pivotal role in the pathogenesis of venous varicose. The identified proteins suggest that the varicose venous wall responds to a stressful condition and that proteolytic degradation of the cytoskeleton, inflammation and apoptosis of smooth muscle cells may be part of the response. Larger studies are required to confirm the potential and clinical role of the identified proteins.