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Homo sapiens isolate:Heart biopsy

ABSTRACT: Left Ventricular Gene Expression in Patients with Heart Failure and Preserved Ejection Fraction

PROVIDER: PRJNA879763 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24421155_1.fastq.gz	Fastqsanger.gz
	SRR24421155_2.fastq.gz	Fastqsanger.gz
	SRR24421156_1.fastq.gz	Fastqsanger.gz
	SRR24421156_2.fastq.gz	Fastqsanger.gz
	SRR24421157_1.fastq.gz	Fastqsanger.gz

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Circulating microRNAs are candidate markers of heart failure and differentiate between heart failure with reduced vs preserved left ventricular ejection fraction.

Project description:In this study, we compared the expression profiles of circulating miRNAs in blood samples from controls and patients with heart ailment. Subject with no past history of heart failure/disease are considered as controls. The patients were classified according to the percentage of left ventricular ejection fraction. Patients were grouped as heart failure with reduced (hfREF) and preserved (hfPEF) left ventricular ejection fraction. Employing miRNA microarray, we identified 'signature miRNAs' in peripheral blood samples that distinguished Heart failure from the non-heart failure controls, as well as those of hfREF and hfPEF groups.

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Project description:The microtubule (MT) cytoskeleton can provide a mechanical resistance that can impede the motion of contracting cardiomyocytes. Yet a role of the MT network in human heart failure is unexplored. Here we utilize mass spectrometry to characterize changes to the cytoskeleton in human heart failure. Proteomic analysis of left ventricle tissue reveals a consistent upregulation and stabilization of intermediate filaments and MTs in human heart failure. This dataset includes left ventricular (LV) myocardium from 34 human hearts – either non-failing (NF) or failing hearts. NF hearts are subdivided into normal or compensated hypertrophy (cHyp), while failing hearts are subdivided into ischemic cardiomyopathy (ICM), dilated cardiomyopathy (DCM), and hypertrophic cardiomyopathy with preserved or reduced ejection fraction (HCMpEF and HCMrEF, respectively). Further details on patient classification and in vivo parameters on each heart are listed in sample details.txt.

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Project description:Heart failure affects 2–3% of adult Western population. Prevalence of heart failure with preserved left ventricular (LV) ejection fraction (HFpEF) increases. Studies suggest HFpEF patients to have altered myocardial structure and functional changes such as incomplete relaxation and increased cardiac stiffness. We hypothesised that patients undergoing elective coronary bypass surgery (CABG) with HFpEF characteristics will show distinctive gene expression compared to patients with normal LV physiology. Myocardial biopsies for mRNA expression analysis were obtained from sixteen patients with LV ejection fraction ≥ 45%. Five out of 16 patients (31%) had echocardiographic characteristics and increased NTproBNP levels indicative of HFpEF and this group was used as HFpEF proxy, while 11 patients had Normal LV physiology. Utilising principal component analysis, the gene expression data clustered into two groups, corresponding to HFpEF proxy and Normal physiology, and 743 differentially expressed genes were identified. The associated top biological functions were cardiac muscle contraction, oxidative phosphorylation, cellular remodelling and matrix organisation. Our results also indicate that upstream regulatory events, including inhibition of transcription factors STAT4, SRF and TP53, and activation of transcription repressors HEY2 and KDM5A, could provide explanatory mechanisms to observed gene expression differences and ultimately cardiac dysfunction in the HFpEF proxy group. <br> Sequencing data from clinical patients fall under GDPR regulations of sharing of personal data and will be made available through EGA-SE.

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Project description:Heart failure (HF) impacts 2-3% of adults in the West, with prevalence rising with age. This condition, leading to high mortality and morbidity, increasingly involves HF with preserved left ventricular (LV) ejection fraction (HFpEF) in the aging population, having a similar stable prognosis as HF with reduced LVEF (HFrEF). However, HFpEF lacks many evidence-based therapies, partly due to its distinct pathophysiology compared to HFrEF. Molecularly, heart failure shows distinct gene expression changes, indicative of varying diseases. Prior research, including our early report from the CABG-PREFERS study, shows gene expression differences in HFpEF and normal hearts, although studies are limited. Both HFpEF and HFrEF patients exhibit altered LV myocardial structure and function, often affecting the right ventricle (RV) secondarily. In the CABG-PREFERS sub-study, part of the PREFERS programme, we classified patients by LVEF, structural abnormalities, diastolic dysfunction, and NT-proBNP levels into HFpEF physiology, HFrEF physiology, and normal LV function groups. Our hypothesis suggests gene expression and transcriptomic variations between LV and RV, and between HFpEF, HFrEF, and normal LV function, providing insights into different HF phenotypes and guiding future therapies.

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