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December 1, 2020Open Access

Transcriptional regulation profiling reveals disrupted lipid metabolism in failing hearts with a pathogenic phospholamban mutation

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Why the study?

The PLN R14del mutation causes various cardiomyopathies and life-threatening ventricular arrhythmias, motivating an investigation into the influence of epigenetic changes from a multi-dimensional perspective.

Population

PLN R14del patients and donor controls

Comparison

Cardiac tissue of PLN R14del patients vs donors

Design

Multi-omics translational case-control study

Key result

The PLN R14del mutation in failing hearts was associated with downregulation of key transcription factor regulators in fatty acid oxidation and disrupted mitochondrial morphology compared to controls.

Authors

JPJiayi PeiNankai UniversityRMRenée G. C. MaasUtrecht UniversityENEma NagyovaUtrecht University

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Overview

Suggests metabolic targets in PLN R14del cardiomyopathy; hypothesis-generating from animal data, requiring human validation.

Study Design

Type

Observational

Structured PICO

P
Population
Patients with genetic cardiomyopathy due to the PLN R14del mutation from a Dutch founder cohort, compared to donor controls.
E
Exposure
Multi-omics profiling (H3K27ac ChIPseq, RNA-seq), immunofluorescence staining, and transmission electron microscopy
C
Comparator
Donor cardiac tissue (controls)
O
Outcome
Differentially acetylated promoters and enhancers, differentially expressed genes, and morphological changes in mitochondria and lipid dropletssurrogate

Multi-omics profiling of PLN R14del hearts reveals disrupted lipid metabolism and mitochondrial morphology, highlighting the role of epigenetic changes in this genetic cardiomyopathy.

Cite This Study

Pei et al. (2020) conducted an observational in Genetic cardiomyopathy due to PLN R14del mutation. PLN R14del mutation vs. Controls (donors) was evaluated on Epigenetic changes, differential gene expression, and mitochondrial lipid abnormalities. The PLN R14del mutation in failing hearts was associated with downregulation of key transcription factor regulators in fatty acid oxidation and disrupted mitochondrial morphology compared to controls.

synapsesocial.com/papers/6a21486f079a8e689f02e748https://doi.org/10.1101/2020.11.30.402792
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