Poster Presentation Australia and New Zealand Society for Extracellular Vesicles Conference 2025

Extracellular Vesicle mRNA Profiles from Hypertrophic Cardiomyocytes Reveal Disease-Specific Signatures and Potential for Biomarker-Based Diagnostics (#108)

Benyapa Tangruksa 1 2 , Cottrell Tamessar 2 , Hadi Valadi 1 , Sepideh Hagvall 2 , Dario Melguizo Sanchis 2 , Jane Synnergren 2 3
  1. Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden
  2. University of Skövde, Skövde, Sweden
  3. Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden

Extracellular vesicles (EV) are nanovesicles secreted by cells that encapsulate RNA, proteins, and lipids reflective of their physiological state [1]. Owing to  their stability in biofluids and cell-specific cargo, EVs are increasingly recognized as promising biomarkers [2]. Nevertheless, their diagnostic relevance in cardiac hypertrophy, which is a major risk factor for heart failure is not yet fully established.

Aim: This study investigates whether exosomes derived from hypertrophic cardiomyocytes exhibit disease-specific mRNA signatures that could serve as non-invasive biomarkers for cardiac hypertrophy.

Methods: Human iPSC-derived cardiomyocytes (hiPSC-CMs) were exposed to Endothelin-1 (ET-1) to induce hypertrophy. EVs were isolated from conditioned media collected 24 hours post-stimulation. RNA from both EVs and parent cells was extracted and analyzed by RNA-sequencing. Differentially expressed genes (DEGs) were identified by comparing ET-1-treated cells/exosomes with untreated controls.

Results: EVs from ET-1-stimulated hiPSC-CMs displayed elevated levels of established hypertrophic markers including NPPA, NPPB, CTGF, ACTA1, THBS1, TGFB1, EDN1 and EDNRA. A substantial number of DEGs were found in both the parental cells and their EVs, many associated with clinical phenotypes such as “cardiac enlargement”. Transcriptomic analysis revealed significant enrichment of pathways related to cardiac hypertrophy signaling and actin cytoskeleton regulation. Notably, there was a strong overlap between the mRNA of EVs and their parent cells, supporting the notion that EVs faithfully reflect the transcriptional state of their source.

Conclusion: EVs released by hypertrophic cardiomyocytes harbor unique and clinically relevant mRNA signatures. These results highlight the potential of EVs as non-invasive biomarkers for the diagnosing and monitoring of cardiac hypertrophy.

Future studies will focus on validating these EV mRNA signatures in biofluids from cardiac hypertrophy patients and evaluating their potential for early diagnosis and disease monitoring in clinical settings.

[1] Zhang E. et. al. (2023) Acta Pharm Sin B. 2023 May; 13(5): 1789–1827.

[2] Zhang L., et. al. (2024) Medicine (Baltimore) 2024 Apr 26;103(17):e37994.