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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 of 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 through cardiomyocyte-specific adeno-associated virus 9 demonstrated an ability to improve heart function and morphology. Pathological staining showed that overexpressing 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 could mediate CRR and supported the development of therapeutics for overexpressing in promoting CRR.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.123.011504 | DOI Listing |
Cardiovasc Res
September 2025
Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University in Saint Louis, St. Louis, MO, USA.
Aims: Although the ability of the heart to adapt to environmental stress has been studied extensively, the molecular and cellular mechanisms responsible for cardioprotection are not yet fully understood. In this study, we sought to elucidate these mechanisms for cytoprotection using a model of stress-induced cardiomyopathy.
Methods And Results: We administered Toll-like receptor (TLR) agonists or diluent to wild-type mice and assessed for cardioprotection against injury from a high intraperitoneal dose of isoproterenol (ISO) administered 7 days later.
PLoS One
September 2025
Department of Cardiology, Fuzhou University Affiliated Provincial Hospital, Fujian Provincial Hospital, Fuzhou, Fujian, China.
Introduction: Kidney stone disease is associated with numerous cardiovascular risk factors. However, the findings across studies are non-uniformly consistent, and the control of confounding variables remains suboptimal. This study aimed to investigate the association between kidney stone and cardiovascular disease.
View Article and Find Full Text PDFJACC Case Rep
September 2025
Pericardial Disease Program, MedStar Heart and Vascular Institute, Washington, District of Columbia, USA.
Background: Pericardial involvement is common in systemic lupus erythematosus (SLE) and can lead to recurrent episodes. B cell-targeted therapies are commonly used in the treatment of SLE pericarditis. The management of recurrent lupus pericarditis refractory to B cell-targeted therapy remains challenging.
View Article and Find Full Text PDFJACC Case Rep
September 2025
Division of Academic Affairs and Research, Orlando Regional Medical Center, Orlando, Florida, USA. Electronic address:
Background: Tachycardia-induced cardiomyopathy (TICM) is typically reversible with rhythm control, but individual susceptibility remains poorly understood and may reflect genetic predisposition.
Case Summary: A 66-year-old woman with paroxysmal atrial fibrillation (AF) presented with new-onset heart failure. Genetic testing identified a likely pathogenic heterozygous ABCC9 gene variant (c.
Cardiol Rev
September 2025
Departments of Medicine and Cardiology, Westchester Medical Center and New York Medical College, Valhalla, NY.
Heart failure (HF) is a complex clinical syndrome marked by impaired contractility, adverse remodeling, and dysregulated intracellular signaling. Protein kinases are central regulators of cardiac function, modulating calcium handling, gene transcription, hypertrophy, and apoptosis through phosphorylation of target proteins. In HF, chronic activation of kinases such as protein kinase A, protein kinase C, calcium/calmodulin-dependent kinase II, mitogen-activated protein kinases, protein kinase B, and Rho-associated protein kinase contributes to progressive cardiac dysfunction.
View Article and Find Full Text PDF