Effects of voluntary exercise on epigenetic regulation and vascular properties in a model of dyslipidemia

Exercise is known to delay the apparition of cardiovascular diseases associated with various risk factors; the underlying mechanisms are, however, poorly understood. We tested the hypothesis that voluntary exercise induces changes in DNA methylation profile as well as functional changes on the vasculature. Three month old severly dyslipidemic (LDLR−/−, hApoB+/+) male mice (SD) and their wild type (WT) controls were offered access, or not, to a running wheel for 3 months of voluntary physical training (PT). DNA was extracted from the gracilis muscle and the DNA methylation profile of target genes was generated using EpiTYPER from Sequenom. Vascular reactivity was assessed in a pressure myograph on isolated femoral arteries. PT and dyslipidemia both induced changes in the methylation profile of CpG islands near the promoter of the target genes including Sod2, Gpx1 and Ptgis. Sensitivity to acetylcholine (ACh) was reduced in SD mice. This reduction was rescued by PT. Therefore, PT was beneficial to mice by preventing the endothelial dysfunction induced by dyslipidemia, possibly by regulating gene expression via an epigenetic mechanism. Supported by CIHR MOP14496.