Overexpression of ATP5F1A in Cardiomyocytes Promotes Cardiac Reverse Remodeling.
Circ Heart Fail
; 17(7): e011504, 2024 Jul.
Article
in En
| MEDLINE
| ID: mdl-38910562
ABSTRACT
BACKGROUND:
The mechanism of cardiac reverse remodeling (CRR) mediated by the left ventricular assist device remains unclear. This study aims to identify the specific cell type responsible for CRR and develop the therapeutic target that promotes CRR.METHODS:
The nuclei were extracted from the left ventricular tissue of 4 normal controls, 4 CRR patients, and 4 no cardiac reverse remodeling patients and then subjected to single-nucleus RNA sequencing for identifying key cell types responsible for CRR. Gene overexpression in transverse aortic constriction and dilated cardiomyopathy heart failure mouse model (C57BL/6J background) and pathological staining were performed to validate the results of single-nucleus RNA sequencing.RESULTS:
Ten cell types were identified among 126â 156 nuclei. Cardiomyocytes in CRR patients expressed higher levels of ATP5F1A than the other 2 groups. The macrophages in CRR patients expressed more anti-inflammatory genes and functioned in angiogenesis. Endothelial cells that elevated in no cardiac reverse remodeling patients were involved in the inflammatory response. Echocardiography showed that overexpressing ATP5F1A through cardiomyocyte-specific adeno-associated virus 9 demonstrated an ability to improve heart function and morphology. Pathological staining showed that overexpressing ATP5F1A could reduce fibrosis and cardiomyocyte size in the heart failure mouse model.CONCLUSIONS:
The present results of single-nucleus RNA sequencing and heart failure mouse model indicated that ATP5F1A could mediate CRR and supported the development of therapeutics for overexpressing ATP5F1A in promoting CRR.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ventricular Remodeling
/
Myocytes, Cardiac
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Disease Models, Animal
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Heart Failure
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Mice, Inbred C57BL
Limits:
Animals
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Female
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Humans
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Male
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Middle aged
Language:
En
Journal:
Circ Heart Fail
Journal subject:
ANGIOLOGIA
/
CARDIOLOGIA
Year:
2024
Document type:
Article