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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Qian, Yongjiang Xiong, Shizheng Li, Lihua Sun, Zhen Zhang, Lili Yuan, Wei Cai, Honghua Feng, Guoquan Wang, Xiaoguang Yao, Haipeng Gao, Yun Guo, Li Wang, Zhongqun |
| Abstract | Background Diabetic macroangiopathy has been the main cause of death and disability in diabetic patients. The mechanisms underlying smooth muscle cell transformation and metabolic reprogramming other than abnormal glucose and lipid metabolism remain to be further explored. Method Single-cell transcriptome, spatial transcriptome and spatial metabolome sequencing were performed on anterior tibial artery from 11 diabetic patients with amputation. Multi-omics integration, cell communication analysis, time series analysis, network analysis, enrichment analysis, and gene expression analysis were performed to elucidate the potential molecular features. Result We constructed a spatial multiomics map of diabetic blood vessels based on multiomics integration, indicating single-cell and spatial landscape of transcriptome and spatial landscape of metabolome. At the same time, the characteristics of cell composition and biological function of calcified regions were obtained by integrating spatial omics and single cell omics. On this basis, our study provides favorable evidence for the cellular fate of smooth muscle cells, which can be transformed into pro-inflammatory chemotactic smooth muscle cells, macrophage-like smooth muscle cells/foam-like smooth muscle cells, and fibroblast/chondroblast smooth muscle cells in the anterior tibial artery of diabetic patients. The smooth muscle cell phenotypic transformation is driven by transcription factors net including KDM5B, DDIT3, etc. In addition, in order to focus on metabolic reprogramming apart from abnormal glucose and lipid metabolism, we constructed a metabolic network of diabetic vascular activation, and found that HNMT and CYP27A1 participate in diabetic vascular metabolic reprogramming by combining public data. Conclusion This study constructs the spatial gene-metabolism map of the whole anterior tibial artery for the first time and reveals the characteristics of vascular calcification, the phenotypic transformation trend of SMCs, and the transcriptional driving network of SMCs phenotypic transformation of diabetic macrovascular disease. In the perspective of combining the transcriptome and metabolome, the study demonstrates the activated metabolic pathways in diabetic blood vessels and the key genes involved in diabetic metabolic reprogramming. Graphical abstract |
| Related Links | https://cardiab.biomedcentral.com/counter/pdf/10.1186/s12933-024-02458-x.pdf |
| Ending Page | 21 |
| Page Count | 21 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 14752840 |
| DOI | 10.1186/s12933-024-02458-x |
| Journal | Cardiovascular Diabetology |
| Issue Number | 1 |
| Volume Number | 23 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2024-10-12 |
| Access Restriction | Open |
| Subject Keyword | Diabetes Angiology Cardiology Diabetic macroangiopathy Spatial multiomics Calcification characteristics Metabolic reprogramming Transcriptional control |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cardiology and Cardiovascular Medicine Internal Medicine Endocrinology, Diabetes and Metabolism |
| Journal Impact Factor | 8.5/2023 |
| 5-Year Journal Impact Factor | 8.9/2023 |
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