Abstract
Hypertrophic cardiomyopathy (HCM) is characterized by unexplained left ventricular hypertrophy. HCM is often hereditary, but our knowledge of the mechanisms leading from mutation to phenotype is incomplete. The transcriptional expression patterns in the myocar - dium of HCM patients may contribute to understanding the mechanisms that drive and stabilize the hypertrophy. Cardiac myectomies/biopsies from 8 patients with hypertrophic obstructive cardiomyopathy (HOCM) and 5 controls were studied with whole genome Illumina microarray gene expression (detecting 18 189 mRNA). When comparing HOCM myocardium to controls, there was significant transcriptional down-regulation of the MYH6, EGR1, APOB and FOS genes, and significant transcriptional up-regulation of the ACE2, JAK2, NPPA (ANP), APOA1 and HDAC5 genes. The transcriptional regulation revealed both pro- and anti-hypertrophic mechanisms. The pro-hypertrophic response was explained by the transcriptional down-regulation of MYH6, indicating that the switch to the fetal gene program is maintained, and the transcriptional up-regulation of JAK2 in the JAK-STAT pathway. The anti-hypertrophic response was seen as a transcriptional down-regulation of the immediate early genes (IEGs), FOS and EGR1, and a transcriptional up-regulation of ACE2 and HDAC5. This can be interpreted as a transcriptional endogenous protection system in the heart of the HOCM patients, neither growing nor suppressing the already hypertrophic myocardium.
Highlights
Hypertrophic cardiomyopathy (HCM) is characterized by cardiac hypertrophy of the septum and/or left ventricular walls in the absence of other pro-hypertrophic diseases.[1]
The aim of this study was to examine the transcriptional expression in the myocardium of patients with the heart of the hypertrophic obstructive caro diomyopathy (HOCM) patients, neither grow- In HCM, cardiac hypertrophy often progress- symptomatic HOCM in an attempt to explain ing nor suppressing the already hypertrophic es for a number of years and subsides, as the mechanisms that drive and maintain the myocardium
Lacking the support of longitudinal data, we present a hypothesis that when expressions of pro- and anti hypertrophic genes are in equilibrium, a sette, sub-family A (ABCA1) (Figure 1)
Summary
Hypertrophic cardiomyopathy (HCM) is characterized by cardiac hypertrophy of the septum and/or left ventricular walls in the absence of other pro-hypertrophic diseases.[1] The disease is often monogenetic, caused by mutations in sarcomeric genes in approximately 56% of cases.[2] At the cellular level, there is an increase in cardiomyocyte size, myocyte disarray and fibrosi.[3,4] HCM is associated with an increased risk of mortality and
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