Hypertrophied cardiomyocytes from patients with aortic valve stenosis exhibited significantly reduced expression of EPHB1, indicating impaired intercellular crosstalk with endothelial cells.
Observational (n=19)
Single-nucleus transcriptomics of human hypertrophic hearts reveals that reduced endothelial-cardiomyocyte crosstalk via the EFNB2-EPHB1 pathway contributes to pathological hypertrophy.
Pathological cardiac hypertrophy is a leading cause of heart failure, but knowledge of the full repertoire of cardiac cells and their gene expression profiles in the human hypertrophic heart is missing. Here, by using large-scale single-nucleus transcriptomics, we present the transcriptional response of human cardiomyocytes to pressure overload caused by aortic valve stenosis and describe major alterations in cardiac cellular crosstalk. Hypertrophied cardiomyocytes had reduced input from endothelial cells and fibroblasts. Genes encoding Eph receptor tyrosine kinases, particularly EPHB1, were significantly downregulated in cardiomyocytes of the hypertrophied heart. Consequently, EPHB1 activation by its ligand ephrin (EFN)B2, which is mainly expressed by endothelial cells, was reduced. EFNB2 inhibited cardiomyocyte hypertrophy in vitro, while silencing its expression in endothelial cells induced hypertrophy in co-cultured cardiomyocytes. Our human cell atlas of the hypertrophied heart highlights the importance of intercellular crosstalk in disease pathogenesis and provides a valuable resource.
Nicin et al. (Mon,) conducted a observational in Aortic valve stenosis with cardiac hypertrophy (n=19). Hypertrophied cardiomyocytes from patients with aortic valve stenosis exhibited significantly reduced expression of EPHB1, indicating impaired intercellular crosstalk with endothelial cells.