Overexpression ofin Cardiomyocytes Promotes Cardiac Reverse Remodeling.

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 126 156 nuclei. Cardiomyocytes in CRR patients expressed higher levels ofthan 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 overexpressingthrough cardiomyocyte-specific adeno-associated virus 9 demonstrated an ability to improve heart function and morphology. Pathological staining showed that overexpressingcould 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 thatcould mediate CRR and supported the development of therapeutics for overexpressingin promoting CRR.