DNA Methylation and Gene Expression Profiling Reveal MFAP5 as a Regulatory Driver of Extracellular Matrix Remodeling in Varicose Vein Disease

Epigenomics. 2018 Aug;10(8):1103-1119. doi: 10.2217/epi-2018-0001. Epub 2018 Aug 2.

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.

Keywords: DNA methylation; MFAP5; extracellular matrix; gene expression; systems biological analysis; varicose vein(s); vascular remodeling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Contractile Proteins / genetics*
  • DNA Methylation
  • Extracellular Matrix*
  • Female
  • Gene Expression Profiling
  • Glycoproteins / genetics*
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Male
  • Middle Aged
  • Saphenous Vein
  • Varicose Veins / genetics*

Substances

  • Contractile Proteins
  • Glycoproteins
  • Intercellular Signaling Peptides and Proteins
  • MAGP2 protein, human