DNMT3A silencing RASSF1A promotes cardiac fibrosis through upregulation of ERK1/2

Epigenetic Therapy for the Treatment of Hypertension-Induced Cardiac Hypertrophy and Fibrosis

“…Therapeutic intervention with 5-aza restored RASSAF1A expression and reduced expression of profibrotic markers. 37 A mouse model of myocardial infarction and a norepinephrine-induced model of cardiac hypertrophy also alluded to protective effects of inhibiting DNA methylation with 5-aza. 38,39 In the recent study by Xiao et al, the authors report that norepinephrine-induced cardiac hypertrophy was associated with DNA hypermethylation and an increase in cardiac levels of DNMTs.…”

Epigenetic regulation in heart failure

“…DNMT3A and B are responsible for de novo methylation patterns [90]. DNMT3A has been reported to play a role in the expression of signaling elements in HF, such as ERK1/2 [91]. Pathological cardiac remodeling is accompanied by activation of genes normally expressed during fetal development.…”

Dnmt3a-mediated inhibition of Wnt in cardiac progenitor cells improves differentiation and remote remodeling after infarction

“…Moreover, in human cardiac tissue, profibrotic changes induced by prolonged hypoxia during MI are associated with a global DNA hypermethylation and increased expression of Dnmt1 and Dnmt3b enzymes (42). Indeed, Dnmt3-induced hypermethylation of antifibrotic genes, such as THY-1 (43) or RASSF1A (44), was shown to contribute to fibroblast activation and fibrogenesis. Therefore, miR-29a overexpression, as observed in this study, could also affect cardiac fibrosis by targeting Dnmt3a/b, propagating Dnmt3 downregulation in surrounding cells.…”