Role of TPM2 in Pediatric Restrictive Cardiomyopathy: Insights from Single-Nucleus RNA Sequencing and Proteomic Analysis

Restrictive cardiomyopathy (RCM) is an uncommon pediatric condition characterised by diastolic dysfunction caused by myocardial stiffness, with preserved systolic function in the early stage. Its pathogenesis is linked to genetic mutations, metabolic defects, or fibrosis, but this process remains incompletely understood. Bioinformatics analysis indicated a crucial role of tropomyosin 2 (TPM2) in pediatric RCM. Using single-nucleus RNA sequencing (snRNA-seq) and proteomics, we identified molecular alterations in RCM hearts compared with controls, with a notable finding that TPM2 expression was markedly reduced in RCM patients. Functional assays showed that TPM2 knockdown in H9C2 cells promoted cell cycle progression (from G0/G1 to S phase), increased apoptosis, and enhanced cell migration. Subsequent western blot analysis confirmed alterations in cyclin-D1 and epithelial-mesenchymal transition (EMT) - related proteins following TPM2 silencing. These findings suggest that TPM2 may act as a cardioprotective factor and biomarker for pediatric RCM, thereby providing new therapeutic targets for this severe condition.