Abstract
Epigenetic changes induced by histone demethylases play an important role in differentiation and pathological changes in cardiac cells. However, the role of the jumonji family of demethylases in the development of cardiac hypertrophy remains elusive. In this study, the presence of different histone demethylases in cardiac cells was evaluated after hypertrophy was induced with neurohormones. A cell line from rat cardiomyocytes was used as a biological model. The phenotypic profiles of the cells, as well as the expression of histone demethylases, were studied through immunofluorescence, transient transfection, western blot, and qRT-PCR analysis after inducing hypertrophy by angiotensin II and endothelin-1. An increase in fetal gene expression (ANP, BNP, and β-MHC) was observed in cardiomyocytes after treatment with angiotensin II and endothelin-1. A significant increase in JMJD2A expression, but not in UTX or JMJD2C expression, was observed. When JMJD2A was overexpressed in cardiomyocytes through transient transfection, the effect of neurohormones on fetal cardiac gene expression was increased. We conclude that JMJD2A plays a principal role in the regulation of fetal cardiac genes, which increase in expression during the pathological hypertrophic process.
Highlights
Cardiac cells undergo hypertrophic growth in response to physiological events such as pregnancy and exercise
The fetal gene expression levels that usually increase with the induction of hypertrophy were evaluated and an increase in atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and β-myosin heavy chain (β-MHC) was observed in H9C2 cells after treatment with angiotensin II (Ang II) and ET-1
In order to recognize the impact of neurohormones on the expression and localization of JMJD2A in the cells, an immunofluorescence assessment was performed in H9C2 cardiomyocytes
Summary
Cardiac cells undergo hypertrophic growth in response to physiological events such as pregnancy and exercise. When hemodynamic stress is a consequence of pathologies such as diabetes mellitus type 2, cardiac ischemia, obesity, or hypertension, cardiac cells undergo genetic and epigenetic changes that stimulate a pathology-induced stress program that includes increased expression of brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP), and β-myosin heavy chain (β-MHC), which accomplish pathological and adaptive roles [1,2,3]. Changes in methylation of the lysine residues in the N- terminal tails of histones H3 and H4 are responsible for controlling gene expression [6,7,8]. A balance of the methylation/demethylation of lysine residues in histones is important for gene expression and genomic integration [9, 10]. Evidence suggests that the deregulation of these lysine methylation properties may play a causative role in promoting congenital heart diseases and adult cardiac hypertrophy [13, 14]
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