Chamber-enriched gene expression profiles in failing human hearts with reduced ejection fraction.
Female
Fibroblasts
/ metabolism
Gene Expression Profiling
Gene Regulatory Networks
Heart Atria
/ physiopathology
Heart Failure
/ metabolism
Heart Ventricles
/ metabolism
Hospitalization
Humans
Male
Middle Aged
Myocardium
/ metabolism
Myocytes, Cardiac
/ metabolism
Necrosis
Oxidative Stress
Prognosis
Signal Transduction
Stroke Volume
/ physiology
Transcription, Genetic
Transcriptome
Ventricular Dysfunction, Left
/ metabolism
Ventricular Function, Left
/ physiology
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
04 06 2021
04 06 2021
Historique:
received:
06
11
2020
accepted:
17
05
2021
entrez:
5
6
2021
pubmed:
6
6
2021
medline:
16
11
2021
Statut:
epublish
Résumé
Heart failure with reduced ejection fraction (HFrEF) constitutes 50% of HF hospitalizations and is characterized by high rates of mortality. To explore the underlying mechanisms of HFrEF etiology and progression, we studied the molecular and cellular differences in four chambers of non-failing (NF, n = 10) and HFrEF (n = 12) human hearts. We identified 333 genes enriched within NF heart subregions and often associated with cardiovascular disease GWAS variants. Expression analysis of HFrEF tissues revealed extensive disease-associated transcriptional and signaling alterations in left atrium (LA) and left ventricle (LV). Common left heart HFrEF pathologies included mitochondrial dysfunction, cardiac hypertrophy and fibrosis. Oxidative stress and cardiac necrosis pathways were prominent within LV, whereas TGF-beta signaling was evident within LA. Cell type composition was estimated by deconvolution and revealed that HFrEF samples had smaller percentage of cardiomyocytes within the left heart, higher representation of fibroblasts within LA and perivascular cells within the left heart relative to NF samples. We identified essential modules associated with HFrEF pathology and linked transcriptome discoveries with human genetics findings. This study contributes to a growing body of knowledge describing chamber-specific transcriptomics and revealed genes and pathways that are associated with heart failure pathophysiology, which may aid in therapeutic target discovery.
Identifiants
pubmed: 34088950
doi: 10.1038/s41598-021-91214-2
pii: 10.1038/s41598-021-91214-2
pmc: PMC8178406
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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