title: DNA methylation in cardiac fibrosis: new advances and perspectives.
abstract: Cardiac fibrosis is characterized by net accumulation of extracellular matrix (ECM) proteins in the cardiac interstitium, and contributes to both systolic and diastolic dysfunction in many cardiac pathophysiologic conditions. More specifically, cardiac fibroblasts are activated by a variety of pathological stimuli, thereby undergoing proliferation, differentiation to myofibroblasts, and production of various cytokines and ECM proteins. Thus, understanding the biological processes of cardiac fibroblasts will provide novel insights into the underlying mechanisms of cardiac fibrosis. DNA methylation is an important epigenetic mechanism, which often occurs in response to environmental stimuli and is crucial in regulating gene expression. The aberrant methylation of CpG island promoters of selected genes is the prominent epigenetic mechanism by which gene transcription can be effectively silenced. Aberrant hypermethylation of a few selected genes such as RASSF1A plays an important role in facilitating fibrotic fibroblast activation and in driving fibrosis. In this review we will discuss the mechanisms of DNA methylation and their implications for cardiac fibroblasts activation and fibrosis. Control of DNA methylation may serve as a new strategy for anti-fibrotic therapy.
authors.affiliation: Department of Cardiothoracic Surgery, The Second Hospital of Anhui Medical University, Hefei 230601, China; Cardiovascular Research Center, Anhui Medical University, Hefei 230601, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Tao
authors.affiliation: Department of Pharmacology, The Second Hospital of Anhui Medical University, Hefei 230601, China; School of Pharmacy, Anhui Medical University, Hefei 230032, China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Yang
authors.affiliation: Department of Cardiothoracic Surgery, The Second Hospital of Anhui Medical University, Hefei 230601, China; Cardiovascular Research Center, Anhui Medical University, Hefei 230601, China. Electronic address: ayskh3@hotmail.com.
authors.forename: Kai-Hu
authors.initials: KH
authors.lastname: Shi
authors.affiliation: Department of Scientific and Educational, The Second Hospital of Anhui Medical University, Hefei 230032, China. Electronic address: zydengsy@163.com.
authors.forename: Zi-Yu
authors.initials: ZY
authors.lastname: Deng
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei 230032, China. Electronic address: yncs01@hotmail.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D019175:DNA Methylation; D005347:Fibroblasts / Q000378:metabolism; D005355:Fibrosis; D006801:Humans; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*
keywords: Cardiac fibroblasts; Cardiac fibrosis; DNA methylation; Extracellular matrix; Gene expression