Genetics and epigenetics of arrhythmia and heart failure

Abstract

Heart failure (HF) is the end stage of several pathological cardiac conditions including myocardial infarction, cardiac hypertrophy and hypertension. Various molecular and cellular mechanisms are involved in the development of HF. At the molecular level, the onset of HF is associated with reprogramming of gene expression, including downregulation of the alpha-myosin heavy chain (α-MHC) gene and sarcoplasmic reticulum Ca 2+ ATPase genes and reactivation of specific fetal cardiac genes such as atrial natriuretic factor and brain natriuretic peptide. These deviations in gene expression result in structural and electrophysiological changes, which eventually progress to HF. Cardiac arrhythmia is caused by altered conduction properties of the heart, which may arise in response to ischemia, inflammation, fibrosis, aging or from genetic factors. Because changes in the gene transcription program may have crucial consequences as deteriorated cardiac function, understanding the molecular mechanisms involved in the process has become a priority in the field. In this context, various studies besides having identified different DNA methylation patterns in HF patients, have also focused on specific disease processes and their underlying mechanisms, also introducing new concepts such as epigenomics. This review highlights specific genetic mutations associated with the onset and progression of HF, also providing an introduction to epigenetic mechanisms such as histone modifications, DNA methylation and RNA-based modification, and highlights the relation between epigenetics, arrhythmogenesis and HF.

Association of the insertion allele of the common ACE gene polymorphism with type 2 diabetes mellitus among Kuwaiti cardiovascular disease patients

“…35,36 A recent study by Rangel et al demonstrated an interaction between DNA methylation and the ACE I/D polymorphism. 37 The DD genotype was found to be associated with a decrease in DNA methylation, which was associated with higher ACE activity.…”

Proliferation of rat cardiac stem cells is induced by 2, 3, 5, 4′-tetrahydroxystilbene-2-O-β-d-glucoside in vitro

“…HCN2 and HCN4 channels are present in the sinus node and regulate the pacemaker current I f and heart rate [1,4,7]. Abnormalities in HCN channels are also associated with MI-induced tachycardia [51]. Connexin 43 is a basic component of the gap junction and is involved in mediating electrical and chemical signals between cardiomyocytes in the cardiac conduction system and working cardiac muscle (atrium and ventricle) [5,9].…”

Are Epigenetic Features Essential in Advance of Heart Failure Phenotypes?

“…Altered miRNA signature risk of CV death [32][33][34][35][36][37] . Whether interactions between features of transcriptomics, proteomics and metabolomics are specifically for HFrEF and HFpEF remains still not clear.…”