ArticleThe Journal of clinical investigation2018
Endothelial pyruvate kinase M2 maintains vascular integrity.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
55 citing papers in PubMed, 87 citations in OpenAlex.
- Targeting Pyruvate Kinase M2: Signal Transduction Pathways and Exploration of Cancer Therapeutic Strategies.The AAPS journal · 2026Review
- PKM2 preconditioning protects endothelial cells from pyroptosis and BBB disruption via NRF2/TRX/TXNIP signaling in neonatal hypoxic-ischemic brain injury.Journal of neuroinflammation · 2026Article
- Metabolic Symbiosis Between Cancer Cells and Endothelial Cells: A Key Driver of Tumor Angiogenesis.Advances in experimental medicine and biology · 2026Review
- Alpha-ketoglutarate mitigates insulin resistance and metabolic inflexibility in a mouse model of Ataxia-Telangiectasia.Nature communications · 2025Article
- PKM2 regulates angiogenic activation via ANGPT2 in endothelial cells.Scientific reports · 2025Article
- Vascular leakage during circulatory failure: physiopathology, impact and treatments.Annals of intensive care · 2025Review
- PKM2-mediated metabolic reprogramming of microglia in neuroinflammation.Cell death discovery · 2025Review
- Palmitic Acid Accelerates Endothelial Cell Injury and Cardiovascular Dysfunction via Palmitoylation of PKM2.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Novel sulfonamides unveiled as potent anti-lung cancer agentsRSC medicinal chemistry · 2024Article
- Neutrophil ALDH2 is a new therapeutic target for the effective treatment of sepsis-induced ARDS.Cellular & molecular immunology · 2024Article
- Targeting PKM2 signaling cascade with salvianic acid A normalizes tumor blood vessels to facilitate chemotherapeutic drug delivery.Acta pharmaceutica Sinica. B · 2024Article
- Capillary malformations.The Journal of clinical investigation · 2024Review
- Protective Factors and the Pathogenesis of Complications in Diabetes.Endocrine reviews · 2024Review
- Reprogramming endothelial cells to empower cancer immunotherapy.Trends in molecular medicine · 2024Review
- Endothelial Cell-Derived Lactate Triggers Bone Mesenchymal Stem Cell Histone Lactylation to Attenuate Osteoporosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Repression of rRNA gene transcription by endothelial SPEN deficiency normalizes tumor vasculature via nucleolar stress.The Journal of clinical investigation · 2023Article
- Pyruvate kinase M2 regulates mitochondrial homeostasis in cisplatin-induced acute kidney injury.Cell death & disease · 2023Article
- Pyruvate Kinase Activity Regulates Cystine Starvation Induced Ferroptosis through Malic Enzyme 1 in Pancreatic Cancer Cells.bioRxiv : the preprint server for biology · 2023Article
- Pharmacological Effects of Astragaloside IV: A Review.Molecules (Basel, Switzerland) · 2023Review
- Metabolic reprogramming, oxidative stress, and pulmonary hypertension.Redox biology · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The M2 isoform of pyruvate kinase (PKM2) is highly expressed in most cancer cells, and has been studied extensively as a driver of oncogenic metabolism. In contrast, the role of PKM2 in nontransformed cells is little studied, and nearly nothing is known of its role, if any, in quiescent cells. We show here that endothelial cells express PKM2 almost exclusively over PKM1. In proliferating endothelial cells, PKM2 is required to suppress p53 and maintain cell cycle progression. In sharp contrast, PKM2 has a strikingly different role in quiescent endothelial cells, where inhibition of PKM2 leads to degeneration of tight junctions and barrier function. Mechanistically, PKM2 regulates barrier function independently of its canonical activity as a pyruvate kinase. Instead, PKM2 suppresses NF-kB and its downstream target, the vascular permeability factor angiopoietin 2. As a consequence, loss of endothelial cell PKM2 in vivo predisposes mice to VEGF-induced vascular leak, and to severe bacteremia and death in response to sepsis. Together, these data demonstrate new roles of PKM2 in quiescent cells, and highlight the need for caution in developing cancer therapies that target PKM2.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.