Evidence map›Paper›PMID 40646595›Full record

ArticleCardiovascular diabetology2025

Glyoxalase-1 overexpression attenuates arterial wall stiffening in diabetic mice.

Margarita G Pencheva, Eline Berends, Koen W F van der Laan, Alessandro Giudici, Petra Niessen, Jean L J M Scheijen, Philippe Vangrieken, Peter Leenders, Tammo Delhaas, Florian Caiment and 7 more

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In one paragraph

Article in Cardiovascular diabetology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Margarita G PenchevaDepartment of Internal Medicine, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Universiteitssingel 50, 6229ER, Maastricht, The Netherlands.
Eline BerendsDepartment of Internal Medicine, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Universiteitssingel 50, 6229ER, Maastricht, The Netherlands.
Koen W F van der LaanDepartment of Biomedical Engineering, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
Alessandro GiudiciDepartment of Biomedical Engineering, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
Petra NiessenDepartment of Internal Medicine, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Universiteitssingel 50, 6229ER, Maastricht, The Netherlands.
Jean L J M ScheijenDepartment of Internal Medicine, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Universiteitssingel 50, 6229ER, Maastricht, The Netherlands.
Philippe VangriekenDepartment of Internal Medicine, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Universiteitssingel 50, 6229ER, Maastricht, The Netherlands.
Peter LeendersDepartment of Pharmacology and Toxicology, Cardiovascular Research Institute Maastricht (CARIM), MHeNs, Mental Health and Neuroscience Research Institute, Maastricht University, Maastricht, The Netherlands.
Tammo DelhaasDepartment of Biomedical Engineering, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
Florian CaimentDepartment of Translational Genomics, GROW Research Institute for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands.
Martina KutmonMaastricht Centre for Systems Biology (MaCSBio), Maastricht University, Maastricht, The Netherlands.
Fabiola M TrujilloDepartment of Translational Genomics, GROW Research Institute for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands.
Kristiaan WoutersDepartment of Internal Medicine, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Universiteitssingel 50, 6229ER, Maastricht, The Netherlands.
Sébastien FoulquierDepartment of Pharmacology and Toxicology, Cardiovascular Research Institute Maastricht (CARIM), MHeNs, Mental Health and Neuroscience Research Institute, Maastricht University, Maastricht, The Netherlands.
Bart Spronck *Department of Biomedical Engineering, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
Koen D Reesink *Department of Biomedical Engineering, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
Casper G SchalkwijkDepartment of Internal Medicine, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Universiteitssingel 50, 6229ER, Maastricht, The Netherlands. c.schalkwijk@maastrichtuniversity.nl.

Funding

European Union's Horizon 2020 954798
6 · The paper itself

Abstract

aimsDiabetes is a leading cause of mortality worldwide, primarily due to cardiovascular diseases (CVD). Arterial stiffness is a CVD predictor and is associated with increased mortality in diabetic individuals. In diabetes, the formation and accumulation of methylglyoxal (MGO), a highly reactive glycolysis by product and a major precursor in advanced glycation endproducts (AGEs) formation, has been implicated in CVD. In this study, we investigated the role of endogenous MGO in arterial stiffening in a mouse model of type 1 diabetes (T1D) overexpressing the MGO-detoxifying enzyme glyoxalase-1 (GLO1). METHODS AND

resultsDiabetes was induced in C57BL/6 J mice through 5-day streptozotocin injections. 17-week-old control, diabetic, and GLO1-overexpressing diabetic mice were used. Fasting glucose in diabetes and GLO1/diabetes was higher than control. Plasma, urine, and aortic MGO, AGEs, and cross-links were determined using ultra-performance liquid chromatography tandem mass spectrophotometry. MGO was increased in plasma and urine in diabetic mice, while GLO1 decreased MGO in urine. The AGE cross-link pentosidine in aorta was increased in diabetes and ameliorated by GLO1. Tail-cuff blood pressure and carotid-femoral pulse wave velocity were measured preceding euthanasia, and did not differ between groups. Descending thoracic aorta ex vivo passive biaxial arterial wall biomechanics were measured and diabetes showed elevated ex vivo PWV, which was attenuated by GLO1 overexpression. Material viscoelasticity was decreased in diabetes and normalised by GLO1 overexpression. Second harmonic generation imaging demonstrated a predominant axial orientation of diabetic collagen fibres, while GLO1/diabetes led to a uniform orientation. When comparing GLO1/diabetes and diabetes, bulk RNA sequencing revealed 137 differentially expressed genes affecting extracellular matrix organisation, cell-cell and cell-matrix communication and interaction pathways.

conclusionIn an animal model of T1D, GLO1 overexpression attenuates arterial stiffening at the underlying material levels, by modifying collagen ultrastructure and viscoelastic properties. Targeting MGO may provide a novel approach to prevent arterial T1D stiffening.

Indexed as

Diabetes Mellitus, ExperimentalDiabetes Mellitus, Type 1Diabetic AngiopathiesLactoylglutathione LyaseVascular StiffnessAnimalsAortaBiomarkersBlood GlucoseGlycation End Products, AdvancedMaleMiceMice, Inbred C57BLMice, TransgenicPyruvaldehydeUp-RegulationBiomarkersBlood GlucoseGlo1 protein, mouseGlycation End Products, AdvancedLactoylglutathione LyasePyruvaldehyde

Identifiers

PMID40646595
PMCPMC12247429

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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Registered trials

None linked

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 Socratic graph.