Changes in the leukocyte methylome and its effect on cardiovascular-related genes after exercise

Article

Denham, Joshua, O'Brien, Brendan J., Marques, Francine Z. and Charchar, Fadi J.. 2015. "Changes in the leukocyte methylome and its effect on cardiovascular-related genes after exercise." Journal of Applied Physiology. 118 (4), pp. 475-488. https://doi.org/10.1152/japplphysiol.00878.2014
Article Title

Changes in the leukocyte methylome and its effect on cardiovascular-related genes after exercise

ERA Journal ID3161
Article CategoryArticle
AuthorsDenham, Joshua, O'Brien, Brendan J., Marques, Francine Z. and Charchar, Fadi J.
Journal TitleJournal of Applied Physiology
Journal Citation118 (4), pp. 475-488
Number of Pages14
Year2015
PublisherAmerican Physiological Society
Place of PublicationUnited States
ISSN1522-1601
8750-7587
Digital Object Identifier (DOI)https://doi.org/10.1152/japplphysiol.00878.2014
Web Address (URL)https://journals.physiology.org/doi/full/10.1152/japplphysiol.00878.2014
Abstract

Physical exercise has proven cardiovascular benefits, yet there is no clear understanding of the related molecular mechanisms leading to this. Here we determined the beneficial epigenetic effects of exercise after sprint interval training, a form of exercise known to improve cardiometabolic health. We quantified genome-wide leukocyte DNA methylation of 12 healthy young (18–24 yr) men before and after 4 wk (thrice weekly) of sprint interval training using the 450K BeadChip (Illumina) and validated gene expression changes in an extra seven subjects. Exercise increased subjects' cardiorespiratory fitness and maximal running performance, and decreased low-density lipoprotein cholesterol concentration in conjunction with genome-wide DNA methylation changes. Notably, many CpG island and gene promoter regions were demethylated after exercise, indicating increased genome-wide transcriptional changes. Among genes with DNA methylation changes, epidermal growth factor (EGF), a ligand of the epidermal growth factor receptor known to be involved in cardiovascular disease, was demethylated and showed decreased mRNA expression. Additionally, we found that in microRNAs miR-21 and miR-210, gene DNA methylation was altered by exercise causing a cascade effect on the expression of the mature microRNA involved in cardiovascular function. Our findings demonstrate that exercise alters DNA methylation in circulating blood cells in microRNA and protein-coding genes associated with cardiovascular physiology.

ANZSRC Field of Research 2020310504. Epigenetics (incl. genome methylation and epigenomics)
310505. Gene expression (incl. microarray and other genome-wide approaches)
420702. Exercise physiology
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Byline AffiliationsFederation University
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