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. 2024 Sep 14;45(35):3292-3295.
doi: 10.1093/eurheartj/ehae472.

Single-nucleus RNA sequencing identifies cell-type-specific effects of sodium-glucose co-transporter 2 inhibitors in human myocardial slices

Kevin Schmidt  1   2   3 , Maximilian Fuchs  2   3 , Natalie Weber  1   4 , Christopher Werlein  5 , Jan D Schmitto  4   6 , Fabio Ius  4   6 , Arjang Ruhparwar  4   6 , Christian Bär  1   2   3   4 , Jan Fiedler  1   2   3 , Thomas Thum  1   4
Affiliations

Single-nucleus RNA sequencing identifies cell-type-specific effects of sodium-glucose co-transporter 2 inhibitors in human myocardial slices

Kevin Schmidt et al. Eur Heart J. .
No abstract available

Keywords: Cardiovascular diseases; Heart failure; Human living myocardial slices; Single-nucleus RNA sequencing; Sodium-glucose co-transporter 2 inhibitors.

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Figures

Figure 1
Figure 1
Cell-type–specific impacts of sodium-glucose co-transporter 2 inhibitors ex vivo underline cardiovascular benefits in heart failure patients. (A) Information of patients from whom tissue pieces were obtained for this study. (B) Uniform manifold approximation and projection plot of sequenced single nuclei from miniaturized living myocardial slices treated with dapagliflozin (DAPA), empagliflozin (EMPA), or respective dimethyl sulfoxide control (top left). Cell-type distribution for each of the three different donors is indicated on the right (top). Expression levels of representative marker genes of each identified cluster (bottom). The ‘unknown’ cluster showed high levels of cell stress-related genes and was excluded from further analyses. (C) Differentially expressed genes in each cell type in response to DAPA or EMPA treatment (averages from all donors). The cut-offs for average fold change (FC) and adjusted P-value were set at 1.5 and .05, respectively. (D) Venn diagrams overlapping differentially expressed genes in the cardiomyocyte fraction in response to DAPA and EMPA (top). Average FCs of parallel regulated genes (bottom). (E) Top 10 overrepresented terms in differentially expressed genes from outlined databases (left). Enrichment analysis of extracellular matrix-associated genes in the mural cell population of miniaturized living myocardial slices upon EMPA treatment (right). (F) Identified cellular communication networks in the sequencing dataset upon respective treatments using the CellChat database. BP, biological processes; CC, cellular component; DORV, double outlet right ventricle; ECM, extracellular matrix; FDR, false discovery rate; GO, gene ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes; LVEF, left ventricular ejection fraction; MF, molecular function; TGA, transposition of the great arteries; UMAP, uniform manifold approximation and projection.
See this image and copyright information in PMC

References

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