ArticleCardiovascular diabetology2024
Genome-scale metabolic network of human carotid plaque reveals the pivotal role of glutamine/glutamate metabolism in macrophage modulating plaque inflammation and vulnerability.
Article in Cardiovascular diabetology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Iron, Copper, and Zinc Dyshomeostasis in Cardiovascular and Cerebrovascular Diseases: Redox Mechanisms, Evidence Levels, and Translational Prospects.International journal of molecular sciences · 2026Review
- Application of glutamine metabolism-related gene signatures in the non-invasive diagnosis of coronary artery disease: integrating bulk and single-cell transcriptomics.Journal of bioenergetics and biomembranes · 2026Article
- Metabolic regulation of macrophage polarization in myocardial infarction: from mechanisms to targeted therapies.Journal of translational medicine · 2026Review
- TRAP5 Inhibition Targeting Scar-Associated Macrophages Ameliorates Acute Kidney Injury to Chronic Kidney Disease Transition.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Glutaminase 1 in Vascular Disease: Linking Metabolic Reprogramming to Atherosclerosis Progression and Stability.Journal of cardiovascular translational research · 2026Review
- Multi-omics analysis identifies gut microbiota-glutamine axis contributing to the pathogenesis of reflux esophagitis.Frontiers in microbiology · 2026Article
- Metabolic profiling reveals potential biomarkers and underlying signaling pathways involved in mindfulness-based cognitive therapy-improved adolescent depression symptoms.EXCLI journal · 2026Article
- Amino acid metabolism modulates macrophage polarization: implications for autoimmune-related diseases.Frontiers in immunology · 2026Review
- Identification of a PRDM1-regulated T cell network to regulate atherosclerotic plaque inflammation.Genome medicine · 2025Article
- Slc7a7 licenses macrophage glutaminolysis for restorative functions in atherosclerosis.Nature metabolism · 2025Article
- Relationship between amino acid metabolism and inflammation in coronary heart disease (Review).International journal of molecular medicine · 2025Review
- Lysosomal Stress in Cardiovascular Diseases: Therapeutic Potential of Cardiovascular Drugs and Future Directions.Biomedicines · 2025Review
- The Interplay Between Immunity, Inflammation and Endothelial Dysfunction.International journal of molecular sciences · 2025Review
- TLR3 and GLUL orchestrate inflammatory and homeostatic imbalance in osteoarthritis.Frontiers in immunology · 2025Article
- Omics Science and Social Aspects in Detecting Biomarkers for Diagnosis, Risk Prediction, and Outcomes of Carotid Stenosis.Biomolecules · 2024Review
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Authors and funding
14 authors.
Funding
Abstract
backgroundMetabolism is increasingly recognized as a key regulator of the function and phenotype of the primary cellular constituents of the atherosclerotic vascular wall, including endothelial cells, smooth muscle cells, and inflammatory cells. However, a comprehensive analysis of metabolic changes associated with the transition of plaque from a stable to a hemorrhaged phenotype is lacking.
methodsIn this study, we integrated two large mRNA expression and protein abundance datasets (BIKE, n = 126; MaasHPS, n = 43) from human atherosclerotic carotid artery plaque to reconstruct a genome-scale metabolic network (GEM). Next, the GEM findings were linked to metabolomics data from MaasHPS, providing a comprehensive overview of metabolic changes in human plaque.
resultsOur study identified significant changes in lipid, cholesterol, and inositol metabolism, along with altered lysosomal lytic activity and increased inflammatory activity, in unstable plaques with intraplaque hemorrhage (IPH+) compared to non-hemorrhaged (IPH-) plaques. Moreover, topological analysis of this network model revealed that the conversion of glutamine to glutamate and their flux between the cytoplasm and mitochondria were notably compromised in hemorrhaged plaques, with a significant reduction in overall glutamate levels in IPH+ plaques. Additionally, reduced glutamate availability was associated with an increased presence of macrophages and a pro-inflammatory phenotype in IPH+ plaques, suggesting an inflammation-prone microenvironment.
conclusionsThis 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.
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