DNA methylation and gene expression profiling reveal MFAP5 as a regulatory driver of extracellular matrix remodeling in varicose vein disease

Mariya A. Smetanina, Alexander E. Kel, Ksenia S. Sevost'Ianova, Igor V. Maiborodin, Andrey I. Shevela, Igor A. Zolotukhin, Philip Stegmaier, Maxim L. Filipenko

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1103-1119
Number of pages17
JournalEpigenomics
Volume10
Issue number8
DOIs
Publication statusPublished - 1 Aug 2018

Keywords

  • DNA methylation
  • extracellular matrix
  • gene expression
  • MFAP5
  • systems biological analysis
  • varicose vein(s)
  • vascular remodeling

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