ArticleCirculation2014
Aldose reductase-mediated phosphorylation of p53 leads to mitochondrial dysfunction and damage in diabetic platelets.
Article in Circulation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
What it found
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The trial behind it
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Who cites it
70 citing papers in PubMed, 126 citations in OpenAlex.
- Trial
- Dose-dependent effects of anthocyanin supplementation on platelet function in subjects with dyslipidemia: A randomized clinical trial.EBioMedicine · 2021Trial
- Procoagulant platelets: linking coagulation and thromboinflammation in cardiovascular disease.Nature reviews. Cardiology · 2026Review
- MicroRNAs in type 2 diabetes mellitus and its cardiovascular complications: mechanistic insights and translational potential.Internal and emergency medicine · 2026Review
- Platelets from older adults exhibit differences in mitochondrial function associated with impaired glucose metabolism.Clinical science (London, England : 1979) · 2026Article
- Platelet mitochondria dysfunction in diabetes mellitus: mechanisms and therapeutic implications.Frontiers in pharmacology · 2026Review
- Acetylsalicylic acid and vorapaxar are less active, while 4-methylcatechol is more active, in type 1 diabetic patients compared to healthy controls.Cardiovascular diabetology · 2025Article
- Iloprost Concentration-Dependently Attenuates Platelet Function and Apoptosis by Elevating PKA Activity.Journal of cellular and molecular medicine · 2025Article
- Sulforaphane attenuates aldose reductase-mediated platelet dysfunction in high glucose-stimulated human platelets via downregulation of the Src/ROS/p53 signaling pathway.Frontiers in nutrition · 2025Article
- Aplastic anemia in association with multiple myeloma: clinical and pathophysiological insights.Leukemia & lymphoma · 2024Article
- Buyang Huanwu decoction ameliorates myocardial injury and attenuates platelet activation by regulating the PI3 kinase/Rap1/integrin α(IIb)β(3) pathway.Chinese medicine · 2024Article
- Platelet, Antiplatelet Therapy and Metabolic Dysfunction-Associated Steatotic Liver Disease: A Narrative Review.Life (Basel, Switzerland) · 2024Review
- The Interplay between Liver Sinusoidal Endothelial Cells, Platelets, and Neutrophil Extracellular Traps in the Development and Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease.Journal of clinical medicine · 2024Review
- The aldose reductase inhibitors AT-001, AT-003 and AT-007 attenuate human keratinocyte senescence.Frontiers in aging · 2024Article
- The Role of Aldose Reductase in Polyol Pathway: An Emerging Pharmacological Target in Diabetic Complications and Associated Morbidities.Current pharmaceutical biotechnology · 2024Review
- Article
- Pyroptosis in cardiovascular diseases: Pumping gasdermin on the fire.Seminars in immunology · 2023Review
- Impact of Physical Exercise on Platelets: Focus on Its Effects in Metabolic Chronic Diseases.Antioxidants (Basel, Switzerland) · 2023Review
- Astragalin ameliorates renal injury in diabetic mice by modulating mitochondrial quality control via AMPK-dependent PGC1α pathway.Acta pharmacologica Sinica · 2023Article
- Targeting the p53 signaling pathway in cancers: Molecular mechanisms and clinical studies.MedComm · 2023Review
10 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
backgroundPlatelet abnormalities are well-recognized complications of diabetes mellitus. Mitochondria play a central role in platelet metabolism and activation. Mitochondrial dysfunction is evident in diabetes mellitus. The molecular pathway for hyperglycemia-induced mitochondrial dysfunction in platelets in diabetes mellitus is unknown. METHODS AND
resultsUsing both human and humanized mouse models, we report that hyperglycemia-induced aldose reductase activation and subsequent reactive oxygen species production lead to increased p53 phosphorylation (Ser15), which promotes mitochondrial dysfunction, damage, and rupture by sequestration of the antiapoptotic protein Bcl-xL. In a glucose dose-dependent manner, severe mitochondrial damage leads to loss of mitochondrial membrane potential and platelet apoptosis (cytochrome c release, caspase 3 activation, and phosphatidylserine exposure). Although platelet hyperactivation, mitochondrial dysfunction, aldose reductase activation, reactive oxygen species production, and p53 phosphorylation are all induced by hyperglycemia, we demonstrate that platelet apoptosis and hyperactivation are 2 distinct states that depend on the severity of the hyperglycemia and mitochondrial damage. Combined, both lead to increased thrombus formation in a mouse blood stasis model.
conclusionsAldose reductase contributes to diabetes-mediated mitochondrial dysfunction and damage through the activation of p53. The degree of mitochondrial dysfunction and damage determines whether hyperactivity (mild damage) or apoptosis (severe damage) will ensue. These signaling components provide novel therapeutic targets for thrombotic complications in diabetes mellitus.
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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.