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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Heart RNA-seq of therapeutic RBM20 antisense oligonucleotide (ASO) treatment in a mouse model of heart failure with preserved ejection fraction (HFpEF)

ABSTRACT: We report the heart RNA-sequencing of control animals and animals of a mouse model of heart failure treated or not with RBM20 antisense oligonucleotide. This study aims to investigate the therapeutic effect of antisense oligonucleotide (ASO)-mediated downregulation of the cardiac splice factor RBM20 in a mouse model of heart failure with preserved ejection fraction. 8-week old wild type and titin N2B KO mice with increased wall stiffness were subcutaneously injected with 50 mg/kg/week RBM20 ASO for 8 weeks. RNA from 4 left ventricles per group were isolated using TRIzol followed by a clean-up with the QIAGEN RNA micro kit. The cDNA libraries were generated using the Illumina TruSeq Stranded mRNA LT Sample Prep Kit and 2x150 paired end sequenced on HiSeq4000. The RNA-Sequencing analysis confirms that RBM20 ASO treatment increased the expression of compliant titin isoforms and improved impaired ventricular filling and cardiac function. RNA-seq confirmed RBM20 dependent isoform changes of known targets such as Titin, Ldb3, Camk2d, and Ank3, and served as a sensitive indicator of potential side effects, largely limited to genes related to the immune response.

INSTRUMENT(S): Illumina HiSeq 4000

ORGANISM(S): Mus musculus

SUBMITTER: Thiago Britto Borges

PROVIDER: E-MTAB-9361 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Heart RNA-seq of therapeutic RBM20 antisense oligonucleotide (ASO) treatment in a mouse model of heart failure with preserved ejection fraction (HFpEF)

Project description:Heart RNA-seq of therapeutic RBM20 antisense oligonucleotide (ASO) treatment in a mouse model of heart failure with preserved ejection fraction (HFpEF)

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Proteomic and phosphoproteomic profiling in heart failure with preserved ejection fraction (HFpEF)

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Therapeutic miR-132 inhibition reverses heart failure

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2017-05-31 | E-MTAB-5389 | biostudies-arrayexpress

Targeting HDAC6 to treat heart failure with preserved ejection fraction, Mouse heart LC-MS with PTMscan

Project description:Heart failure with preserved ejection fraction (HFpEF) poses therapeutic challenges due to the limited treatment options. Building upon our previous research that demonstrates the efficacy of histone deacetylase 6 (HDAC6) inhibition in a genetic cardiomyopathy model, we investigate HDAC6’s role in HFpEF due to their shared mechanisms of inflammation and metabolism. Here, we show that inhibiting HDAC6 with TYA-018 effectively reverses established heart failure and its associated symptoms in HFpEF mouse models. Additionally, in mice lacking the Hdac6 gene, HFpEF progression is delayed and they are resistant to TYA-018’s effects. The efficacy of TYA-018 is comparable to a sodium-glucose cotransporter 2 (SGLT2) inhibitor, and their combination shows enhanced effects. Mechanistically, TYA-018 restores gene expression related to hypertrophy, fibrosis, and mitochondrial energy production in HFpEF heart tissues. Furthermore, TYA-018 also inhibits activation of human cardiac fibroblasts and enhances mitochondrial respiratory capacity in cardiomyocytes. In this work, our findings show that HDAC6 impacts heart pathophysiology and is a promising target for HFpEF treatment.

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Expression analysis of mice hepatic NMuLi cells treated LNA gapmer ASO containing nucleobase modification

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