Abstract 15192: Comprehensive Analysis of DNA Methylation in Physiological Cardiac Hypertrophy
Introduction Physiological cardiac hypertrophy in response to exercise training involves significant transcriptional profile changes. DNA methylation is one epigenetic mechanism which can significantly affect gene transcription. Aberrant DNA methylation have been linked to heart failure and other cardiovascular diseases, however, the role of DNA methylation in physiological cardiac hypertrophy is still unknown.
Method and Result Eight-week old male C57BL/6J mice were randomized into either treadmill running or sedentary control groups. After forty days of intensity-controlled treadmill running, the treadmill-trained mice showed significant cardiac hypertrophy with a 28.0% increase in systolic left ventricular posterior wall thickness (P<0.05) and a 27.2% increase in heart-to-body weight ratio (P<0.05) compared with control mice. We analyzed genome-wide DNA methylation profile of left ventricular in three treadmill-trained mice and three sedentary controls using methylated DNA immunoprecipitation microarray (MeDIP-chip). The number of methylated CpG islands significantly increased in physiological cardiac hypertrophy (3762±500 vs. 2499±299, P=0.02). We identified 741 promoters that were differentially methylated with 634 hypermethylated and 107 hypomethylated in treadmill-trained mice. By integrating the promoter DNA methylation data with the gene expression profiles, we discovered 142 genes that showed both altered DNA methylation patterns and expression levels. Gene ontology analysis of these genes reveals an overrepresentation of gene categories involved in actin filament-based process, cytoskeleton organization and programmed cell death (all P<0.001).
Conclusion Our study offers the first comprehensive analysis of DNA methylation in physiological cardiac hypertrophy and reveals that the expression of many genes involved in cardiac remodeling might be regulated by promoter methylation.
- © 2011 by American Heart Association, Inc.