Chamber-enriched gene expression profiles in failing human hearts with reduced ejection fraction.
Sci Rep
; 11(1): 11839, 2021 06 04.
Article
em En
| MEDLINE
| ID: mdl-34088950
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Disfunção Ventricular Esquerda
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Perfilação da Expressão Gênica
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Insuficiência Cardíaca
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Ventrículos do Coração
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article