Key result
HFpEF links to upregulated extracellular matrix genes without activated proinflammatory pathways across ~480 genes.
Why the study?
The molecular mechanisms and signaling pathways underlying HFpEF are poorly defined, including whether activation of proinflammatory pathways contributes to cardiac fibrosis.
Does the left ventricular transcriptome in patients with HFpEF show activation of profibrotic and proinflammatory signaling pathways compared to controls?
Cross-Sectional (n=30)
No
Does the left ventricular transcriptome in patients with HFpEF show activation of profibrotic and proinflammatory signaling pathways compared to controls?
This study demonstrates that the myocardial substrate of advanced, compensated HFpEF is characterized by pronounced extracellular matrix production and fibrosis, but lacks a persistent tissue-level proinflammatory signature.
BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is increasingly prevalent and has few treatments. The molecular mechanisms and resultant signaling pathways that underlie the development of HFpEF are poorly defined. It has been proposed that activation of proinflammatory pathways plays a role in the development of cardiac fibrosis. The signature of gene expression (transcriptome) of previously validated left ventricular biopsies obtained from patients with HFpEF and matched referent controls allows for an unbiased assessment of proinflammatory and profibrotic signaling pathways and genes. METHODS: Epicardial left ventricular biopsies from stringently selected HFpEF patients (HFpEF, n=16) and referent control patients (CTR, n=14) were obtained during aortocoronary bypass surgery. The subepicardial myocardium was flash-frozen to build a repository that was parallel-processed for RNA sequencing to allow for an unsupervised in-depth comparison of the left ventricular transcriptome. The transcriptome analysis revealed differential expression of 477 genes many of which were involved in profibrotic pathways including extracellular matrix production and posttranslational modification but no proinflammatory signature. CONCLUSIONS: The transcriptome analysis of left ventricular myocardial samples from patients with HFpEF confirms an overabundant extracellular matrix gene expression, the basis of myocardial fibrosis, without a signature of activated proinflammatory pathways or genes.
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Ye et al. (2023) conducted a cross-sectional in Heart failure with preserved ejection fraction (HFpEF) (n=30). Heart failure with preserved ejection fraction (HFpEF) vs. Referent controls with severe coronary artery disease but no hypertension or heart failure was evaluated on Differential expression of left ventricular genes (transcriptome analysis). Transcriptome analysis revealed differential expression of 477 genes in HFpEF patients, confirming overabundant extracellular matrix gene expression without a signature of activated proinflammatory pathways.
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