About: Abstract Objective To explore the transcriptomic differences between patients with hypertrophic cardiomyopathy (HCM) and controls. Patients and Methods RNA was extracted from cardiac tissue flash frozen at therapeutic surgical septal myectomy for 106 patients with HCM and from 39 healthy donor hearts. Expression profiling of 37,846 genes was performed using the Illumina Human HT-12v3 Expression BeadChip. All HCM patients were genotyped for pathogenic variants causing HCM. Technical validation was performed using quantitative real-time PCR (qRT-PCR) and Western blot. This study was started on January 1, 1999 and final analysis was completed on April 20, 2020. Results Overall, 22% of the transcriptome (8443 genes) was expressed differentially between HCM and control tissues. Analysis by genotype revealed that gene expression changes were similar among genotypic subgroups of HCM, with only 4-6% of the transcriptome exhibiting differential expression between genotypic subgroups. qRT-PCR confirmed differential expression in 92% of tested transcripts. Notably, in the context of COVID-19, the transcript for ACE2, a negative regulator of the angiotensin system, was the single most up-regulated gene in HCM (fold-change 3.53, q-value=1.30x10-23), which was confirmed with qRT-PCR in triplicate (fold-change 3.78; p=5.22x10-4), and Western blot confirmed a >5-fold over-expression of ACE2 protein (fold-change 5.34, p=1.66x10-6). Conclusions Over 20% of the transcriptome is expressed differentially between HCM and control tissues. Importantly, ACE2 was the most up-regulated gene in HCM indicating perhaps the heart’s compensatory effort to mount an anti-hypertrophic, anti-fibrotic response. However, given that the SARS-CoV-2 uses ACE2 for viral entry, this 5-fold increase in ACE2 protein may confer increased risk for COVID-19 manifestations and outcomes in patients with increased ACE2 transcript expression and protein levels in the heart.

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About: Abstract Objective To explore the transcriptomic differences between patients with hypertrophic cardiomyopathy (HCM) and controls. Patients and Methods RNA was extracted from cardiac tissue flash frozen at therapeutic surgical septal myectomy for 106 patients with HCM and from 39 healthy donor hearts. Expression profiling of 37,846 genes was performed using the Illumina Human HT-12v3 Expression BeadChip. All HCM patients were genotyped for pathogenic variants causing HCM. Technical validation was performed using quantitative real-time PCR (qRT-PCR) and Western blot. This study was started on January 1, 1999 and final analysis was completed on April 20, 2020. Results Overall, 22% of the transcriptome (8443 genes) was expressed differentially between HCM and control tissues. Analysis by genotype revealed that gene expression changes were similar among genotypic subgroups of HCM, with only 4-6% of the transcriptome exhibiting differential expression between genotypic subgroups. qRT-PCR confirmed differential expression in 92% of tested transcripts. Notably, in the context of COVID-19, the transcript for ACE2, a negative regulator of the angiotensin system, was the single most up-regulated gene in HCM (fold-change 3.53, q-value=1.30x10-23), which was confirmed with qRT-PCR in triplicate (fold-change 3.78; p=5.22x10-4), and Western blot confirmed a >5-fold over-expression of ACE2 protein (fold-change 5.34, p=1.66x10-6). Conclusions Over 20% of the transcriptome is expressed differentially between HCM and control tissues. Importantly, ACE2 was the most up-regulated gene in HCM indicating perhaps the heart’s compensatory effort to mount an anti-hypertrophic, anti-fibrotic response. However, given that the SARS-CoV-2 uses ACE2 for viral entry, this 5-fold increase in ACE2 protein may confer increased risk for COVID-19 manifestations and outcomes in patients with increased ACE2 transcript expression and protein levels in the heart. Goto Sponge NotDistinct Permalink

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Attributes	Values
type	abstract
value	Abstract Objective To explore the transcriptomic differences between patients with hypertrophic cardiomyopathy (HCM) and controls. Patients and Methods RNA was extracted from cardiac tissue flash frozen at therapeutic surgical septal myectomy for 106 patients with HCM and from 39 healthy donor hearts. Expression profiling of 37,846 genes was performed using the Illumina Human HT-12v3 Expression BeadChip. All HCM patients were genotyped for pathogenic variants causing HCM. Technical validation was performed using quantitative real-time PCR (qRT-PCR) and Western blot. This study was started on January 1, 1999 and final analysis was completed on April 20, 2020. Results Overall, 22% of the transcriptome (8443 genes) was expressed differentially between HCM and control tissues. Analysis by genotype revealed that gene expression changes were similar among genotypic subgroups of HCM, with only 4-6% of the transcriptome exhibiting differential expression between genotypic subgroups. qRT-PCR confirmed differential expression in 92% of tested transcripts. Notably, in the context of COVID-19, the transcript for ACE2, a negative regulator of the angiotensin system, was the single most up-regulated gene in HCM (fold-change 3.53, q-value=1.30x10-23), which was confirmed with qRT-PCR in triplicate (fold-change 3.78; p=5.22x10-4), and Western blot confirmed a >5-fold over-expression of ACE2 protein (fold-change 5.34, p=1.66x10-6). Conclusions Over 20% of the transcriptome is expressed differentially between HCM and control tissues. Importantly, ACE2 was the most up-regulated gene in HCM indicating perhaps the heart’s compensatory effort to mount an anti-hypertrophic, anti-fibrotic response. However, given that the SARS-CoV-2 uses ACE2 for viral entry, this 5-fold increase in ACE2 protein may confer increased risk for COVID-19 manifestations and outcomes in patients with increased ACE2 transcript expression and protein levels in the heart.
Subject	RNA Cardiomyopathy Gene expression Omics RNA splicing Cat diseases RTT Cytoskeletal defects Road traffic management Autosomal dominant disorders Sports medicine Cardiogenetic disorders Roads in the United States
part of	Marked Up-Regulation of ACE2 in Hearts of Patients with Obstructive Hypertrophic Cardiomyopathy: Implications for SARS-CoV-2-Mediated COVID-19
is abstract of	Marked Up-Regulation of ACE2 in Hearts of Patients with Obstructive Hypertrophic Cardiomyopathy: Implications for SARS-CoV-2-Mediated COVID-19
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