ArticleDiabetes2009
Reductive metabolism of AGE precursors: a metabolic route for preventing AGE accumulation in cardiovascular tissue.
Article in Diabetes, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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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.
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Who cites it
53 citing papers in PubMed, 117 citations in OpenAlex.
- Compensatory mechanisms for methylglyoxal detoxification in experimental & clinical diabetes.Molecular metabolism · 2018Trial
- Reactive carbonyl species in health and chronic disease: from methylglyoxal to an integrative network of metabolic regulation.Cardiovascular diabetology · 2026Review
- Glyoxalase 1 is a proadipogenic gene.The Journal of biological chemistry · 2025Article
- Non-enzymatic posttranslational protein modifications in protein aggregation and neurodegenerative diseases.RSC chemical biology · 2025Review
- Dual roles of methylglyoxal in cancer.Frontiers in oncology · 2025Review
- Alleviation of nephropathy during aging as complications of diabetic by natural products.African health sciences · 2024Article
- Review
- An overview on glycation: molecular mechanisms, impact on proteins, pathogenesis, and inhibition.Biophysical reviews · 2024Review
- Protective Factors and the Pathogenesis of Complications in Diabetes.Endocrine reviews · 2024Review
- Molecular Assessment of Methylglyoxal-Induced Toxicity and Therapeutic Approaches in Various Diseases: Exploring the Interplay with the Glyoxalase System.Life (Basel, Switzerland) · 2024Review
- Aldose Reductase (AR) Mediates and Perivascular Adipose Tissue (PVAT) Modulates Endothelial Dysfunction of Short-Term High-Fat Diet Feeding in Mice.Metabolites · 2023Article
- Methylglyoxal in Cardiometabolic Disorders: Routes Leading to Pathology Counterbalanced by Treatment Strategies.Molecules (Basel, Switzerland) · 2023Review
- Analysis of Methylglyoxal Concentration in a Group of Patients with Newly Diagnosed Prediabetes.Biomedicines · 2023Article
- Proteomic alterations associated with residual disease in neoadjuvant chemotherapy treated ovarian cancer tissues.Clinical proteomics · 2022Article
- Effect of vinyl chloride exposure on cardiometabolic toxicity.Environmental toxicology · 2022Article
- Role of the Glyoxalase System in Breast Cancer and Gynecological Cancer-Implications for Therapeutic Intervention: a Review.Frontiers in oncology · 2022Review
- Elevated serum levels of methylglyoxal are associated with impaired liver function in patients with liver cirrhosis.Scientific reports · 2021Article
- The Glyoxalase System in Age-Related Diseases: Nutritional Intervention as Anti-Ageing Strategy.Cells · 2021Review
- The Role of AKR1B10 in Physiology and Pathophysiology.Metabolites · 2021Review
- Glyoxalase System as a Therapeutic Target against Diabetic Retinopathy.Antioxidants (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
objectiveTo examine the role of aldo-keto reductases (AKRs) in the cardiovascular metabolism of the precursors of advanced glycation end products (AGEs). RESEARCH DESIGN AND
methodsSteady-state kinetic parameters of AKRs with AGE precursors were determined using recombinant proteins expressed in bacteria. Metabolism of methylglyoxal and AGE accumulation were studied in human umbilical vein endothelial cells (HUVECs) and C57 wild-type, akr1b3 (aldose reductase)-null, cardiospecific-akr1b4 (rat aldose reductase), and akr1b8 (FR-1)-transgenic mice. AGE accumulation and atherosclerotic lesions were studied 12 weeks after streptozotocin treatment of C57, akr1b3-null, and apoE- and akr1b3-apoE-null mice.
resultsHigher levels of AGEs were generated in the cytosol than at the external surface of HUVECs cultured in high glucose, indicating that intracellular metabolism may be an important regulator of AGE accumulation and toxicity. In vitro, AKR 1A and 1B catalyzed the reduction of AGE precursors, whereas AKR1C, AKR6, and AKR7 were relatively ineffective. Highest catalytic efficiency was observed with AKR1B1. Acetol formation in methylglyoxal-treated HUVECs was prevented by the aldose reductase inhibitor sorbinil. Acetol was generated in hearts perfused with methylglyoxal, and its formation was increased in akr1b4- or akr1b8-transgenic mice. Reduction of AGE precursors was diminished in hearts from akr1b3-null mice. Diabetic akr1b3-null mice accumulated more AGEs in the plasma and the heart than wild-type mice, and deletion of akr1b3 increased AGE accumulation and atherosclerotic lesion formation in apoE-null mice.
conclusionsAldose reductase-catalyzed reduction is an important pathway in the endothelial and cardiac metabolism of AGE precursors, and it prevents AGE accumulation and atherosclerotic lesion formation.
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Registered trials
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