Spatial Multiomics Reveals Metabolic Reprogramming and Calcification Characteristics of Diabetic Macroangiopathy [Spatial Transcriptomics]

BACKGROUND: The diabetic macroangiopathy includes coronary heart disease, cerebrovascular disease and peripheral artery disease. Diabetic macroangiopathy is the main cause of death in diabetic patients. The exact pathogenesis of diabetic macroangiopathy is still not completely clear. METHODS: Single-cell transcriptome, spatial transcriptome, and spatial metabolome sequencing were performed on specimens of the anterior tibial artery from 11 amputated patients for visualization and data analysis through bioinformatics. RESULTS: This study reveals the gene-metabolic network in metabolic reprogramming and calcification characteristics in diabetic macrovasculature. Tissue specificity was found in some metabolic pathways. Alpha-linolenic acid metabolism and linoleic acid metabolism were characteristically enriched in the arteriae externa, and folate biosynthesis was characteristically expressed in calcification region. O-glycan biosynthesis, and primary bile acid biosynthesis are enriched in plaques. The calcification area mainly expresses COL1A2 COL6A2 FN1, MIF, SPP1, TNC as ligands to adjust and control media and plaque. The presence of nuclear enrichment related lesion changes around calcification resulted in activation of chemokine function, erk1/2 function and phenylalanine pathway. CONCLUSIONS: This study is the first to construct a spatial gene-metabolic map of complete blood vessels, which provides a basis for the subsequent exploration of the mechanism and clinical transformation of diabetic macrovascular disease. The clinical samples and related information obtained in this study were all approved by the Ethics Committee of Jiangsu University, and all patients gave written informed consent. They were diagnosed with diabetes according to the diagnostic criteria of China's Guidelines for the Prevention and Treatment of Type 2 Diabetes (2020), and CT of lower limbs showed significant calcification. In addition, patients who received diabetic foot surgery according to the Guidelines for the Prevention and Treatment of Diabetic Foot in China (2019) were included in the study.The fresh tissues isolated from 4 patients were divided into calcified group (n=3) and noncalcified group (n=3) according to the relative position of CT images and vascular stiffness. After dead cells were removed, the samples were sequenced on the NovaSeq 6000 platform.