Aim: To integrate transcriptomic and DNA-methylomic measurements on varicose versus normal veins using a systems biological analysis to shed light on the interplay between genetic and epigenetic factors. Materials & methods: Differential expression and methylation were measured using microarrays, supported by real-time quantitative PCR and immunohistochemistry confirmation for relevant gene products. A systems biological ‘upstream analysis’ was further applied. Results: We identified several potential key players contributing to extracellular matrix remodeling in varicose veins. Specifically, our analysis suggests MFAP5 acting as a master regulator, upstream of integrins, of the cellular network affecting the varicose vein condition. Possible mechanism and pathogenic model were outlined. Conclusion: A coherent model proposed incorporates the relevant signaling networks and will hopefully aid further studies on varicose vein pathogenesis.

Varicose veins of the lower limbs are one of the most common and wide-spread pathology all around the world. What triggers the specific changes in a vein wall still remains unclear as well as what happens in the layers of the vein wall after the disease starts. The aim of the article is to analyze published data and results of researches on epidemiology, genetics, cellular and molecular mechanisms underlying varicose veins pathogenesis. It is now commonly accepted that vein wall changes in patients with varicose veins result from vein-specific inflammation. This process includes leukocytes adhesion to venous endothelium with their subsequent migration into the vein wall and surrounding tissues. Activated leukocytes express a number of molecules that lead to vein wall remodeling and dilation. Comprehensive assessment of the epidemiological data on the prevalence of varicose veins and risk factors, of the findings from genetic studies, of data on molecular-cell interactions as well as results of various surgical interventions in patients with varicose veins, shows that remodeling is a reversible process that can be stopped and reversed by different stimuli including some chemical substances. For the first time in the literature, the authors assume that varicose veins can be successfully cured pharmacologically with no surgical interventions needed.