Genome-scale metabolic network of human carotid plaque reveals the pivotal role of glutamine/glutamate metabolism in macrophage modulating plaque inflammation and vulnerability
Authors' conclusion
This study is the first to establish a robust and comprehensive GEM for atherosclerotic plaque, providing a valuable resource for understanding plaque metabolism. The utility of this GEM was illustrated by its ability to reliably predict dysregulation in the cholesterol hydroxylation, inositol metabolism, and the glutamine/glutamate pathway in rupture-prone hemorrhaged plaques, a finding that may pave the way to new diagnostic or therapeutic measures.
Study context
- Population
- Human atherosclerotic carotid artery plaque; BIKE and MaasHPS datasetsBIKE n = 126 · BIKE 126 · MaasHPS 43
- Comparison
- Plaques with intraplaque hemorrhage vs non-hemorrhaged plaques
- Outcome
- Metabolic changes in IPH+ vs IPH- plaques
Methodological detailsgenome-scale metabolic network reconstruction, integrated mRNA expression and protein abundance datasets, linked to metabolomics data
- Genome-scale metabolic network reconstruction
- Integrated mRNA expression and protein abundance datasets
- Linked to metabolomics data
Main finding
As reported in the abstract
- Significant changes in lipid, cholesterol and inositol metabolism, altered lysosomal lytic activity and increased inflammatory activity in IPH+ vs IPH- plaques
- Conversion of glutamine to glutamate and their flux between cytoplasm and mitochondria notably compromised in hemorrhaged plaques
- Significant reduction in overall glutamate levels in IPH+ plaques
- Reduced glutamate availability associated with increased presence of macrophages and a pro-inflammatory phenotype in IPH+ plaques
Original publication
Genome-scale metabolic network of human carotid plaque reveals the pivotal role of glutamine/glutamate metabolism in macrophage modulating plaque inflammation and vulnerability. Cardiovasc Diabetol. Published 8 July 2024. doi:10.
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