The DOI matches its Crossref record; 71 of the 71 references it cites were found in a registry or an index.
The glycolytic enzyme PKM2 bridges metabolic and inflammatory dysfunction in coronary artery disease
Open accessAbstract
Abnormal glucose metabolism and enhanced oxidative stress accelerate cardiovascular disease, a chronic inflammatory condition causing high morbidity and mortality. Here, we report that in monocytes and macrophages of patients with atherosclerotic coronary artery disease (CAD), overutilization of glucose promotes excessive and prolonged production of the cytokines IL-6 and IL-1β, driving systemic and tissue inflammation. In patient-derived monocytes and macrophages, increased glucose uptake and glycolytic flux fuel the generation of mitochondrial reactive oxygen species, which in turn promote dimerization of the glycolytic enzyme pyruvate kinase M2 (PKM2) and enable its nuclear translocation. Nuclear PKM2 functions as a protein kinase that phosphorylates the transcription factor STAT3, thus boosting IL-6 and IL-1β production. Reducing glycolysis, scavenging superoxide and enforcing PKM2 tetramerization correct the proinflammatory phenotype of CAD macrophages. In essence, PKM2 serves a previously unidentified role as a molecular integrator of metabolic dysfunction, oxidative stress and tissue inflammation and represents a novel therapeutic target in cardiovascular disease.
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Metadata
- Authors
- Shirai, T., Nazarewicz, R. R., Wallis, B. B., Yanes, R. E., Watanabe, R., Hilhorst, M., Tian, L., Harrison, D. G., Giacomini, J. C., Assimes, T. L., Goronzy, J. J., & Weyand, C. M.
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2016-02-29
- Volume
- 213
- Issue
- 3
- Pages
- 337-354
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2296002833
- Cited by
- 543
- References
- 71
- FWCI
- 23.89
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Shirai, T., Nazarewicz, R. R., Wallis, B. B., Yanes, R. E., Watanabe, R., Hilhorst, M., Tian, L., Harrison, D. G., Giacomini, J. C., Assimes, T. L., Goronzy, J. J., & Weyand, C. M. (2016). The glycolytic enzyme PKM2 bridges metabolic and inflammatory dysfunction in coronary artery disease. Journal of Experimental Medicine. https://doi.org/10.1084/jem.20150900
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
