Abstract
Abstract 19037: Metabolomics Reveals Aerobic Glycolysis and 1-Carbon Metabolism as Major Metabolic Signature During Human Platelet Activation
Circulation (New York, N.Y.), Vol.148(Suppl_1)
11/07/2023
DOI: 10.1161/circ.148.suppl_1.19037
Abstract
Abstract only Introduction: Evolving evidence suggests that besides signaling pathways, platelet activation involve a complex interplay between metabolic pathways to support thrombus growth. Selective targeting of metabolic checkpoints may inhibit platelet activation and provide a novel antiplatelet strategy. We examined global metabolic changes that occur during the transition of human platelets from resting to an activated state to identify metabolites and associated pathways that contribute to platelet activation. Methods: We performed metabolic profiling (through Metabolon Inc.) of resting and stimulated human platelet samples. The differential levels analysis, pathway analysis, and PCA were performed using Metaboanalyst. Metascape was used for metabolite network construction. Results: Of the 401 metabolites identified, 202 metabolites were significantly upregulated, and two metabolites were downregulated in activated platelets. Of all the metabolites, lipids scored highly and constituted ~50% of the identification. During activation, aerobic glycolysis supports energy demand and provides glycolytic intermediates required by metabolic pathways. Consistent with this, an important category of metabolites was carbohydrates, particularly the glycolysis intermediates that were significantly upregulated compared to resting platelets. We found that lysophospholipids such as 1-palmitoyl-GPA, 1-stearoyl-GPS, 1-palmitoyl-GPI, 1-stearoyl-GPI, 1-oleoyl-GPI were upregulated in activated platelets. We speculated that platelet activation could be linked to One-carbon (1C) metabolism, a set of biochemical pathways that involve transfer and use of 1C units from amino acids, for cellular processes, including nucleotide and lysophospholipid synthesis. In alignment, based on pathway enrichment and network-based prioritization, the metabolites from amino acid metabolism, including serine, glutamate, and branched-chain amino acids pathway were upregulated in activated platelets, which might be supplemented by the high levels of glycolytic intermediates. Conclusions: Metabolic analysis of resting and activated platelets revealed that aerobic glycolysis and 1-C carbon metabolism are vital to support platelet activation.
Details
- Title: Subtitle
- Abstract 19037: Metabolomics Reveals Aerobic Glycolysis and 1-Carbon Metabolism as Major Metabolic Signature During Human Platelet Activation
- Creators
- Manasa K Nayak - University of IowaMadankumar Ghatge - University of IowaGagan D Flora - University of IowaAnil K Chauhan - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Circulation (New York, N.Y.), Vol.148(Suppl_1)
- DOI
- 10.1161/circ.148.suppl_1.19037
- ISSN
- 0009-7322
- eISSN
- 1524-4539
- Language
- English
- Date published
- 11/07/2023
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984539442402771
Metrics
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