ArticleJCI insight2020
PFKFB3-mediated glycolysis rescues myopathic outcomes in the ischemic limb.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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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.
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Who cites it
28 citing papers in PubMed, 39 citations in OpenAlex.
- HK2 promotes angiogenesis through H3K18 lactylation in peripheral arterial disease.Communications biology · 2026Article
- Glucose Metabolic Enzyme PFKFB3 in Cardiopulmonary Vascular Health and Disease.Circulation research · 2026Review
- Adenosine Triggers an ADK-Dependent Intracellular Signaling Pathway Interacts PFKFB3-Mediated Glycolytic Metabolism to Promote Newly Formed Myofibers Development.International journal of molecular sciences · 2025Article
- Endothelial cell metabolism in cardiovascular physiology and disease.Nature reviews. Cardiology · 2025Review
- Nicotinamide N-methyltransferase inhibition improves limb function in experimental peripheral artery disease.Physiological reports · 2025Article
- Metabolic dysfunction promoted by mitochondrial DNA mutation burden drives retinal degeneration.bioRxiv : the preprint server for biology · 2025Article
- Control of circadian muscle glucose metabolism through the BMAL1-HIF axis in obesity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A 6-Minute Limb Function Assessment for Therapeutic Testing in Experimental Peripheral Artery Disease Models.JACC. Basic to translational science · 2025Article
- Traumatic Skeletal Muscle Injury and Recovery.Advances in experimental medicine and biology · 2025Review
- PFKFB3 ameliorates ischemia-induced neuronal damage by reducing reactive oxygen species and inhibiting nuclear translocation of Cdk5.Scientific reports · 2024Article
- Glycolytic PFKFB3 and Glycogenic UGP2 Axis Regulates Perfusion Recovery in Experimental Hind Limb Ischemia.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- A 6-minute Limb Function Assessment for Therapeutic Testing in Experimental Peripheral Artery Disease Models.bioRxiv : the preprint server for biology · 2024Article
- Review
- A Circular Network of Coregulated L-Threonine and L-Tryptophan Metabolism Dictates Acute Lower Limb Ischemic Injury.International journal of medical sciences · 2024Article
- Deletion of the aryl hydrocarbon receptor in endothelial cells improves ischemic angiogenesis in chronic kidney disease.American journal of physiology. Heart and circulatory physiology · 2024Article
- Single-Nuclei RNA-Sequencing of the Gastrocnemius Muscle in Peripheral Artery Disease.Circulation research · 2023Article
- IGF-1 Therapy Improves Muscle Size and Function in Experimental Peripheral Arterial Disease.JACC. Basic to translational science · 2023Article
- Pentose Pathway Activation Is Superior to Increased Glycolysis for Therapeutic Angiogenesis in Peripheral Arterial Disease.Journal of the American Heart Association · 2023Article
- Hypoxia Resistance Is an Inherent Phenotype of the Mouse Flexor Digitorum Brevis Skeletal Muscle.Function (Oxford, England) · 2023Article
- AAV-mediated expression of PFKFB3 in myofibers, but not endothelial cells, improves ischemic muscle function in mice with critical limb ischemia.American journal of physiology. Heart and circulatory physiology · 2022Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
Abstract
Compromised muscle mitochondrial metabolism is a hallmark of peripheral arterial disease, especially in patients with the most severe clinical manifestation - critical limb ischemia (CLI). We asked whether inflexibility in metabolism is critical for the development of myopathy in ischemic limb muscles. Using Polg mtDNA mutator (D257A) mice, we reveal remarkable protection from hind limb ischemia (HLI) due to a unique and beneficial adaptive enhancement of glycolytic metabolism and elevated ischemic muscle PFKFB3. Similar to the relationship between mitochondria from CLI and claudicating patient muscles, BALB/c muscle mitochondria are uniquely dysfunctional after HLI onset as compared with the C57BL/6 (BL6) parental strain. AAV-mediated overexpression of PFKFB3 in BALB/c limb muscles improved muscle contractile function and limb blood flow following HLI. Enrichment analysis of RNA sequencing data on muscle from CLI patients revealed a unique deficit in the glucose metabolism Reactome. Muscles from these patients express lower PFKFB3 protein, and their muscle progenitor cells possess decreased glycolytic flux capacity in vitro. Here, we show supplementary glycolytic flux as sufficient to protect against ischemic myopathy in instances where reduced blood flow-related mitochondrial function is compromised preclinically. Additionally, our data reveal reduced glycolytic flux as a common characteristic of the failing CLI patient limb skeletal muscle.
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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.