PhD Scientific Days 2025

Poster Session II. - U: Cardiovascular Medicine and Research

Immune Cells Milieu of Fabry Heart Revealed by Spatial Transcriptomics

Name of the presenter

Kovács Sándor

Institute/workplace of the presenter

Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary

Authors

Sándor Dávid Kovács¹, Luca Kamilla Li¹, Júlia Erhardt^1,2, Karolina Schnabel³, Lajos Hegyi², Nóra Fekete⁴, Attila Fintha², László Kőhidai⁴, Péter Reismann³, Éva Pállinger³, Hajnalka Vágó², Csaba Bödör¹, Árpád Ferenc Kovács^1,2

1: Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
2: Heart and Vascular Center, Semmelweis University, Budapest, Hungary
3: Department of Internal Medicine and Oncology, Semmelweis University, Budapest, Hungary
4: Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary

Text of the abstract

Introduction
Fabry disease is the most common lysosomal storage disorder (LSD) caused by the loss or deficient α-galactosidase (AGAL) enzyme due to pathogenic variants in the GLA gene. Chronic inflammation is a hallmark of LSDs, however in certain cases acute on chronic inflammation may develop, leading to acute organ damage.

Aims
Our aim was to analyse an explanted hypertrophied heart via spatial transcriptomics approach to evaluate the immune milieu.

Methods
4 frozen-fixed paraffin embedded tissue samples from a 17-year-old Fabry patient’s heart were prepared for spatial transcriptomics based on 10x Genomics Visium platform. 3’ transcriptomics library preparation and sequencing. It was followed by alignment to GRCh38 using Space Ranger v.3.1.2. Loupe Browser 8.1.2 was used for clustering and gene expression analysis.

Results
Spatial transcriptomics showed an abundant NPPA gene expression (2.28 ± 0.25 mean ±SD fold change) within the subendocardial cardiomyocytes. Both perivascular and infiltrative cardiac resident CD163+ CD14+ macrophages exhibited a high TMSB4X expression ((1.46 ± 0.14 and 1.71 ±0.38 mean ±SD fold change).

Conclusion
Our preliminary results suggest that the immune cell milieu, particularly cardiac resident macrophages, CD3+CD4+ T cells and NK cells may influence the acute organ damage via alterations of immune homeostasis in Fabry disease.

Funding
Hungarian National Research, Development and Innovation Office—NKFIH, OTKA PD_21 138521 and 10x Genomics Prague 2023 grant to Á.F.K.