Circ Genom Precis Med. 2025 Oct 6:e005192. doi: 10.1161/CIRCGEN.125.005192. Online ahead of print.
ABSTRACT
BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a relatively rare but debilitating diagnosis in the pediatric population, and patients with end-stage HCM require heart transplantation. Here, we have examined the transcriptome in ventricular tissue from this patient group to identify cell states and underlying cellular processes unique to pediatric HCM.
METHODS: We performed single-nucleus RNA sequencing on explanted hearts at transplant in 3 pediatric patients with end-stage HCM and compared findings to pediatric control and adult HCM.
RESULTS: We identified distinct underlying cellular processes in cardiomyocytes, fibroblasts, endothelial cells, and myeloid cells compared with controls. Pediatric HCM was enriched in cardiomyocytes exhibiting stressed myocardium gene signatures and underlying pathways associated with cardiac hypertrophy; cardiac fibroblasts exhibited activation signatures and compared with adult patients, exhibited heightened downstream processes associated with fibrosis and a unique, myofibroblast-like cluster with increased metabolic stress and antiapoptotic properties. We noted depletion of tissue-resident macrophages and increased vascular remodeling in endothelial cells in pediatric HCM.
CONCLUSIONS: Our analysis provides the first single-nucleus analysis focused on end-stage pediatric HCM. Fibroblast-mediated cellular processes were the most prominent in pediatric HCM, which had more downstream processes associated with fibrosis than did adult HCM.
PMID:41048033 | DOI:10.1161/CIRCGEN.125.005192
