A novel view to varicose veins pathogenesis: Proteomic profiling suggests a pivotal role of extracellular matrix degradation

Abstract

Introduction Although morphological and anatomical studies indicate that venous wall weakening and subendothelial fibrosis characterize varicose veins (VV), the pathogenesis of VV remains poorly understood. The aim of this study is to obtain protein expression profiles in patients with VV and thereby get a step closer to understanding the pathogenesis of VV. Methods Specimens were obtained from total of 10 patients, that is, from 5 patients undergoing VV surgical stripping and from 5 non-VV patients undergoing bypass surgery. Specimens were collected from the same layers of venous wall. Proteins were extracted from each specimen and analyzed by ion mobility spectrometry (IMS-MS). In total, 1387 were identified and 486 proteins were identified in all samples. From these, 15 proteins were differentially expressed between VV and non-VV samples ( p < .05) and 12 of these showed a fold change >1.5. Results Interestingly, among the differentially expressed proteins, only two proteins were significantly increased in the VV tissue, that is, GAPDH ( p = .028, fold change 2.74), where several proteins involved in maintaining the homeostasis in the extracellular matrix, that is, the CXXC zinc finger protein 5 ( CXXC5) and nucleoporin ( SEH1) were prominently downregulated ( p = .049, fold change 37.8, and p = .040, fold change 3.46). The downregulation in protein expression of CXXC5 and SEH1 as well as upregulation of GAPDH were validated by Western blotting. Conclusion The identified differentially expressed proteins suggest an altered profile of the connective tissue proteins as well as an increased proteolytic enzyme activity which both may be central in the pathophysiology of varicose veins.