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

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

Author information

1
Laboratory of Pharmacogenomics, Institute of Chemical Biology & Fundamental Medicine, Novosibirsk 630090, Russia.
2
Department of Fundamental Medicine, Novosibirsk State University, Novosibirsk 630090, Russia.
3
Department of Research & Development, geneXplain GmbH, Wolfenb├╝ttel D-38302, Germany.
4
Center of New Medical Technologies, Institute of Chemical Biology & Fundamental Medicine, Novosibirsk 630090, Russia.
5
Stem Cell Laboratory, Institute of Chemical Biology & Fundamental Medicine, Novosibirsk 630090, Russia.
6
Chair of Faculty Surgery of the Medical Department, Pirogov Russian National Research Medical University, Moscow 117997, Russia.

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

PMID:
30070582
DOI:
10.2217/epi-2018-0001

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