Spatial Multiomics Reveals Metabolic Reprogramming and Calcification Characteristics of Diabetic Macroangiopathy
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ABSTRACT:
PROVIDER: PRJNA1045029 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26946833_1.fastq.gz | Fastqsanger.gz | |||
| SRR26946833_2.fastq.gz | Fastqsanger.gz | |||
| SRR26946834_1.fastq.gz | Fastqsanger.gz | |||
| SRR26946834_2.fastq.gz | Fastqsanger.gz | |||
| SRR26946835_1.fastq.gz | Fastqsanger.gz |
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Project description: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.
2024-10-16 | GSE248608 | GEO
Project description: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.
2024-10-16 | GSE248609 | GEO
Project description:Spatial Multiomics Reveals Metabolic Reprogramming and Calcification Characteristics of Diabetic Macroangiopathy [Spatial Transcriptomics]
| PRJNA1045028 | ENA
Project description:Spatial Multiomics Reveals Metabolic Reprogramming and Calcification Characteristics of Diabetic Macroangiopathy [scRNA-Seq]
| PRJNA1045032 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-10-16 | GSE248610 | GEO
Project description:Hyperglycemia accelerates calcification of atherosclerotic plaques in diabetic patients, and the prolonged accumulation of advanced glycation end products (AGEs) induced by hyperglycemia may be closely related to the pathogenesis of aortic calcification. However, the mechanisms underlying this association remain unclear. In the current study, we investigated the role of vascular smooth muscle cell nuclear factor 90/110 (NF90/110) in mediating AGEs accumulation and accelerating diabetic atherosclerotic calcification. Using vascular smooth muscle cells (VSMCs), human samples, and mouse models, we found that hyperglycemia-mediated AGEs markedly increased VSMC NF90/110 activation both in human and mouse atherosclerotic calcified tissues with diabetes. Silencing of NF90/110 in vitro and genetic deletion of VSMC NF90/110 in mice decreased obviously AGEs-induced arteriosclerotic calcification. Mechanistically, AGEs increased the activity of NF90, which then enhanced ubiquitination and degradation of AGE receptor 1 (AGER1) by stabilizing the mRNA of E3 ubiquitin ligase, F-box, and WD repeat domain 7 (FBXW7), thus causing the accumulation of more AGEs. Furthermore, AGEs accumulation accelerated diabetic atherosclerotic calcification by inducing VSMC phenotypic changes to osteoblast-like cells, apoptosis, and matrix vesicle release. Collectively, our study demonstrated the effects of VSMC NF90 in mediating the metabolic imbalance of AGEs to accelerate diabetic arteriosclerotic calcification. These novel findings elucidate a pivotal mechanism underlying AGE-induced diabetic atherosclerotic calcification and provide a framework for potential interventions against diabetic vascular complications.
2024-04-02 | GSE253682 | GEO
Project description:Diabetic macroangiopathy is one of the most common serious complications of diabetes. Previous studies indicate that lncRNAs involved in the process of diabetes and another vascular disease. However, their detailed mechanism of the lncRNAs involved in diabetic macroangiopathy has not been well characterized. In the present study, we generated rat models of diabetic macroangiopathy induced by High fat. A total of 15 GK rats was constructed as a test group, along with 15 Wistar rats set as a control group, and thoracic aorta tissue from each group was collected. Whole genomic RNA sequencing was performed on thoracic aorta tissue;3223 novel lncRNAs and 20367 annotated lncRNAs were identified in thoracic aorta samples, and 864 lncRNAs were expressed differently in the test and control groups. Gene ontology term enrichment showed the apparent enrichment of inflammatory response and cell apoptosis, which consistent with the results of H&E Staining, TUNEL Assay, and ELISA; Extensive literature reveals inflammatory response and cell apoptosis play an important role in the process of diabetic macroangiopathy.The results of the present study indicated that lncRNAs, especiallyNrep.bSep08,Col5a1,aSep0,soygee.aSep08-unspliced,NONRATT013247.2,votar.aSep08-unspliced,etc,both participate in and mediate the process of inflammatory response,cell apoptosis.What’s more, Our research provides further insights into the understanding of the basic molecular mechanisms underlying diabetic macroangiopathy.
2020-07-25 | GSE155059 | GEO
Project description:Hyperglycemia accelerates calcification of atherosclerotic plaques in diabetic patients, and the prolonged accumulation of advanced glycation end products (AGEs) induced by hyperglycemia may be closely related to the pathogenesis of aortic calcification. However, the mechanisms underlying this association remain unclear. In the current study, we investigated the role of vascular smooth muscle cell nuclear factor 90/110 (NF90/110) in mediating AGEs accumulation and accelerating diabetic atherosclerotic calcification. Using vascular smooth muscle cells (VSMCs), human samples, and mouse models, we found that hyperglycemia-mediated AGEs markedly increased VSMC NF90/110 activation both in human and mouse atherosclerotic calcified tissues with diabetes. Silencing of NF90/110 in vitro and genetic deletion of VSMC NF90/110 in mice decreased obviously AGEs-induced arteriosclerotic calcification. Mechanistically, AGEs increased the activity of NF90, which then enhanced ubiquitination and degradation of AGE receptor 1 (AGER1) by stabilizing the mRNA of E3 ubiquitin ligase, F-box, and WD repeat domain 7 (FBXW7), thus causing the accumulation of more AGEs. Furthermore, AGEs accumulation accelerated diabetic atherosclerotic calcification by inducing VSMC phenotypic changes to osteoblast-like cells, apoptosis, and matrix vesicle release. Collectively, our study demonstrated the effects of VSMC NF90 in mediating the metabolic imbalance of AGEs to accelerate diabetic arteriosclerotic calcification. These novel findings elucidate a pivotal mechanism underlying AGE-induced diabetic atherosclerotic calcification and provide a framework for potential interventions against diabetic vascular complications.
2024-04-02 | PXD048707 |
Project description:Aims/hypothesis. Ectopic calcification is a typical feature of diabetic vascular disease and resembles an accelerated aging phenotype. We previously found an excess of myeloid calcifying cells (MCCs) in diabetic patients. We herein examined molecular and cellular pathways linking atherosclerotic calcification with calcification by myeloid cells in the diabetic milieu. Methods. We first examined the associations among coronary calcification, MCC levels, and mononuclear cell gene expression in a cross-sectional study of 87 type 2 diabetic patients undergoing elective coronary angiography. Then, we undertook in vitro studies on mesenchymal stem cells (MSCs) and on the THP-1 myeloid cells line to verify the causal relationships of the observed associations. Results. Coronary calcification was associated with 2.8-times higher MCC levels (p=0.037) and 50% elevated expression of the osteogenic gene RUNX2 in mononuclear cells, whereas expression of Sirtuin-7 (SIRT7) was inversely correlated with calcification. In standard differentiation assays of MSCs, SIRT7 knockdown activated the osteogenic program and worsened calcification, especially in the presence of high (20 mM) glucose. In the monocytic cell line THP-1, SIRT7 downregulation drove a pro-calcific phenotype, whereas SIRT7 overexpression prevented high-glucose induced calcification. Through the JAK/STAT pathway, high glucose induced miR-125b-5p, which in turn targeted SIRT7 in myeloid cells and was directly associated with coronary calcification. Conclusions/interpretation. We describe a new pathway elicited by high glucose trough the JAK/STAT cascade, involving regulation of SIRT7 by mir-125b-5p driving calcification by myeloid cells. This pathway is associated with coronary calcification in diabetic patients and may be a target to tackle diabetic vascular disease.
2022-01-15 | GSE193510 | GEO
Project description:Arterial media calcification caused by diabetes is an important cause of vascular calcification. Dipeptidyl peptidase-4 (DPP4) is associated with diabetic arterial media calcification. At the same time, long non-coding RNA(lncRNA) is closely related to the evolution of a variety of cardiovascular diseases, but the involvement of lncRNA in vascular calcification induced by DPP4 has not been reported in details. In this study, we established a model of human aortic smooth muscle cells (HASMCs) calcification induced by DPP4. There was a significant difference in the expression of lncRNAs and mRNAs between normal and calcified vascular smooth muscle cells detected by gene chip technology. Based on the results of microarray detection, we found that lncRNA may be involved in vascular calcification induced by DPP4 through regulating target genes.
2021-12-03 | GSE189923 | GEO