Epigenome-Wide DNA Methylation Profiling in Comparison between Pathological and Physiological Hypertrophy of Human Cardiomyocytes

Physiological and pathological stimuli result in distinct anatomic forms of cardiac hypertrophy, but the head-to-head comparison of molecular regulation between physiological and pathological cardiac hypertrophy is less well understood, especially at the DNA methylation level. We conducted an in vitro study using human cardiomyocyte cell line AC16 exposed to angiotensin II (AngII) and insulin-like growth factor 1 (IGF-1) to mimic pathologically and physiologically hypertrophic heart models, respectively. Whole genome DNA methylation patterns were profiled by the Infinium human MethylationEPIC platform with >850K DNA methylation loci. We detected 194 loci that are significantly differentially methylated after AngII treatment (vs control) with 50.0% hypermethylated, and 206 significant loci after IGF-1 treatment (vs control) with 45.1% hypermethylated (Adjusted P < 0.05). Mapping the significant loci to genes, we identified 158 genes corresponding to AngII treatment and 175 genes to IGF-1 treatment, with 67 genes overlapping between AngII and IGF-1. We conducted an in vitro study using human cardiomyocyte cell line AC16 exposed to angiotensin II (AngII) and insulin-like growth factor 1 (IGF-1) for 12h and 24h to mimic pathologically and physiologically hypertrophic heart models, respectively. Whole genome DNA methylation patterns were profiled by the Infinium human MethylationEPIC platform with >850K DNA methylation loci.