Key result
In diabetic mice, cardiac endothelial cells and cardiomyocytes exhibited altered communication properties, with Angptl4-Cdh5 and Angptl4-Sdc3 ligand-receptor pairs significantly upregulated.
Why the study?
The study was conducted to explore the heterogeneities and communication properties of cardiac cardiomyocytes and endothelial cells in diabetes.
Single-cell sequencing and experimental validation reveal that Angptl4-Cdh5 and Angptl4-Sdc3 pathways mediate altered communication between cardiac endothelial cells and cardiomyocytes in diabetic mice.
Answers are grounded in this paper and cite their sources.
Hypothesis-generating for EC-CM crosstalk in diabetic cardiomyopathy; requires human validation before any clinical consideration.
OBJECTIVE: We aimed to explore the heterogeneities and communication properties of cardiac CMs and ECs in diabetes. METHODS: GSE213337 dataset was retrieved from NCBI Gene Expression Omnibus, containing the single-cell RNA sequencing data of hearts from the control and streptozotocin-induced diabetic mice. Cell cluster analysis was performed to identify the cell atlas. Data of CMs and ECs were extracted individually for re-cluster analysis, functional enrichment analysis and trajectory analysis. Cell communication analysis was conducted to explore the altered signals and significant ligand-receptor interactions. RESULTS: Eleven cell types were identified in the heart tissue. CMs were re-clustered into four subclusters, and cluster 4 was dominant in diabetic condition and enriched in cellular energy metabolism processes. ECs were re-clustered into six subclusters, and clusters 2, 4 and 5 were dominant in the diabetic condition and mainly enriched in cellular energy metabolism and lipid transport processes. The cellular communication network was altered in the diabetic heart. ECs dominated the overall signaling and notably increased the ANGPTL and SEMA4 signals in the diabetic heart. Four significant ligand-receptor pairs implicating the two signals contributed to the communication between ECs and other cell types, including Angptl1-(Itga1 + Itgb1), Angptl4-Cdh5, Angptl4-Sdc3, and Sema4a-(Nrp + Plxna2). The ligand Angptl4 engaged in ECs-CMs communication in a paracrine manner. CONCLUSION: Single-cell sequencing analysis revealed heterogeneities of ECs and CMs in diabetes, Angptl4-Cdh5 and Angptl4-Sdc3 were involved in the communication between ECs and CMs in diabetes.
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Wen et al. (2025) studied Diabetic cardiomyopathy (n=12). Streptozotocin-induced diabetes vs. Sodium citrate control was evaluated on Cellular communication properties and ligand-receptor interactions between cardiac endothelial cells and cardiomyocytes. In diabetic mice, cardiac endothelial cells and cardiomyocytes exhibited altered communication properties, with Angptl4-Cdh5 and Angptl4-Sdc3 ligand-receptor pairs significantly upregulated.
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