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Down-Regulation of Ephrin-B1 in Left Ventricular Non-Compaction

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Article Type Research Article
Subject Medicine Group
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Andrea Frustaci*, Antonio Russo M , Alessandro De Luca, Davide Scarselli, Maria Cecilia D Asdia Aurora Polvani, Emanuela Frustaci, Manuel Belli, Luigi Sansone, Nicola Galea, Livia Marchitelli and Romina Verardo
Issue: Volume7-Issue4
Pages: 1-14
Received: 2026-04-20
Accepted: 2026-04-28
Published: 2026-04-29

Abstract

Background: Left Ventricular Non-Compaction (LVNC) is a rare cardiomyopathy with incompletely understood pathophysiological mechanisms. Ephrin-B1 (Ep), a key protein of cardiomyocyte lateral junctions, may play a role in cell cohesion. This study is aimed to characterize structural alterations of lateral junctions, quantify Ep expression, and identify genetic variants associated with LVNC.
Methods: We conducted an observational study on 13 patients from 12 independent families diagnosed with LVNC using cardiac magnetic resonance and endomyocardial biopsy. Histological, ultrastructural, and molecular analyses, including Ep expression and whole exome sequencing, were performed. Myocardial PCR was obtained for viral agents screening.
Results: Cardiomyocyte disconnection at lateral junctions was observed in all cases, ranging up to complete cell separation, while intercalated discs were preserved. The resulting intramural channels were extensively devoid of endothelial layer with frequent over-imposition of thrombotic material. Ep expression was reduced by 64% compared with controls (6229 ± 3197 vs 21451 ± 5054 densitometric units; absolute difference ?15222; p < 0.001). Lymphocytic myocarditis was present in 6 of 13 patients (46%; approximate CI 19–75%). Cardiomyopathy-related genetic variants were identified in 8 of 13 patients (61.5%). The EPHA2 polymorphism rs3754334 was found in 11/13 patients (85%) compared with 28% in the European population. No viral genomes were detected at myocardial PCR.
Conclusions: LVNC is characterized by lateral cardiomyocyte disconnection and marked down-regulation of Ep. Intramural channels often lacks of endothelium and are side of thrombus formation. Virus-negative myocarditis coexists in 46% of cases. These findings may contribute to arrhythmias, thromboembolism, and heart failure.
What is already known on this topic?
LVNC is a rare cardiomyopathy with unclear pathogenesis and heterogeneous genetic background. The cellular basis of cardiomyocyte disorganization and the role of lateral junction proteins are poorly understood.
What this study adds?
LVNC is characterized by cardiomyocyte disconnection at lateral junctions with marked Ephrin-B1 down-regulation. A high prevalence of virus-negative myocarditis (46%) and cardiomyopathy-related variants, including EPHA2 polymorphism enrichment, was identified.
How this study might affect research, practice or policy?
These findings support assessing myocardial inflammation and junctional integrity in LVNC. They suggest potential benefit of immunosuppressive therapy in selected cases and provide new targets for diagnosis and treatment.

FullText HTML FullText PDF DOI: 10.37871/jbres2296 Crossmark

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Copyright

© 2026 Frustaci A, et al. Distributed under Creative Commons CC-BY 4.0 Creative CommonsAttribution

How to cite this article

Frustaci A, Russo AM, Luca AD, Scarselli D, Asdia MCD, Polvani A, Frustaci E, Belli M, Sansone L, Galea N, Marchitelli L, Verardo R. Down-Regulation of Ephrin-B1 in Left Ventricular Non-Compaction. J Biomed Res Environ Sci. 2026 Apr 29; 7(4): 14. Doi: 10.37872/jbres2296

Subject area(s)

PathologyCardiovascular DiseasesClinical Cardiology

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