Left Ventricular Gene Expression in Heart Failure With Preserved Ejection Fraction-Profibrotic and Proinflammatory Pathways and Genes.
abnormalities
cardiac fibrosis
diastolic dysfunction
heart failure with preserved ejection fraction
inflammation
Journal
Circulation. Heart failure
ISSN: 1941-3297
Titre abrégé: Circ Heart Fail
Pays: United States
ID NLM: 101479941
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
pmc-release:
01
08
2024
medline:
17
8
2023
pubmed:
15
8
2023
entrez:
15
8
2023
Statut:
ppublish
Résumé
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. 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 average patient age was 67±10 years. When compared with controls, patients with HFpEF were hypertensive with a higher body mass index (kg/m 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.
Sections du résumé
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.
RESULTS
The average patient age was 67±10 years. When compared with controls, patients with HFpEF were hypertensive with a higher body mass index (kg/m
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.
Identifiants
pubmed: 37582166
doi: 10.1161/CIRCHEARTFAILURE.123.010395
pmc: PMC10430768
mid: NIHMS1903421
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e010395Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL122744
Pays : United States
Commentaires et corrections
Type : CommentIn
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