Heart RNA-seq of control mice and a mouse model of cardiometabolic heart failure (HFpEF) treated with Rbm20 antisense oligonucleotides

We report the heart RNA-sequencing of control animals (C57BL/6N genetic background, wild type) and animals of a mouse model of cardiometabolic heart failure (HFpEF) treated or not with RBM20 antisense oligonucleotide. HFpEF was induced using a 2-hit regimen, in which male mice were fed with a high-fat diet (D12492, Research Diet Inc) and L-NAME 0.5g/L (nitric oxide synthase inhibitor) in drinking water, beginning at 3 months of age and continue for 22 weeks. Control male mice were fed with a control diet (D12450K, Research Diet Inc) and water without L-NAME This study aims to investigate the therapeutic effect of antisense oligonucleotide (ASO)-mediated downregulation of the cardiac splice factor RBM20 in HFpEF-like conditions. Adult mice were subcutaneously injected with 25 mg/kg/week for 6 weeks. RNA from left ventricular tissue was isolated using TRIzol followed by a clean-up with the QIAGEN RNA micro kit, cDNA libraries were generated using the Illumina TruSeq Stranded mRNA Sample Prep Kit 2x150 single-end sequenced on Illumina NovaSeq X Plus. The RNA-Sequencing analysis confirms that RBM20 ASO treatment increased the expression of compliant titin isoforms and improved diastolic function, even in the context of cardiometabolic stress.