Pyridoxamine prevents increased atherosclerosis by intermittent methylglyoxal spikes in the aortic arches of ApoE-/- mice
Methylglyoxal (MGO) is a reactive glucose metabolite linked to diabetic cardiovascular disease (CVD). MGO levels surge during intermittent hyperglycemia. We hypothesize that these MGO spikes contribute to atherosclerosis, and that pyridoxamine as a MGO quencher prevents this injury. To study this, w...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-02-01
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| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332222016006 |
| _version_ | 1811177282979495936 |
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| author | Nordin M.J. Hanssen Chris Tikellis Raelene J. Pickering Dragana Dragoljevic Man Kit Sam Lee Tomasz Block Jean LJM Scheijen Kristiaan Wouters Toshio Miyata Mark E. Cooper Andrew J. Murphy Merlin C. Thomas Casper G. Schalkwijk |
| author_facet | Nordin M.J. Hanssen Chris Tikellis Raelene J. Pickering Dragana Dragoljevic Man Kit Sam Lee Tomasz Block Jean LJM Scheijen Kristiaan Wouters Toshio Miyata Mark E. Cooper Andrew J. Murphy Merlin C. Thomas Casper G. Schalkwijk |
| author_sort | Nordin M.J. Hanssen |
| collection | DOAJ |
| description | Methylglyoxal (MGO) is a reactive glucose metabolite linked to diabetic cardiovascular disease (CVD). MGO levels surge during intermittent hyperglycemia. We hypothesize that these MGO spikes contribute to atherosclerosis, and that pyridoxamine as a MGO quencher prevents this injury. To study this, we intravenously injected normoglycemic 8-week old male C57Bl6 ApoE-/- mice with normal saline (NS, n = 10) or 25 µg MGO for 10 consecutive weeks (MGOiv, n = 11) with or without 1 g/L pyridoxamine (MGOiv+PD, n = 11) in the drinking water. We measured circulating immune cells by flow cytometry. We quantified aortic arch lesion area in aortic roots after Sudan-black staining. We quantified the expression of inflammatory genes in the aorta by qPCR. Intermittent MGO spikes weekly increased atherosclerotic burden in the arch 1.8-fold (NS: 0.9 ± 0.1 vs 1.6 ± 0.2 %), and this was prevented by pyridoxamine (0.8 ± 0.1 %). MGOiv spikes increased circulating neutrophils and monocytes (2-fold relative to NS) and the expression of ICAM (3-fold), RAGE (5-fold), S100A9 (2-fold) and MCP1 (2-fold). All these changes were attenuated by pyridoxamine. This study suggests that MGO spikes damages the vasculature independently of plasma glucose levels. Pyridoxamine and potentially other approaches to reduce MGO may prevent excess cardiovascular risk in diabetes |
| first_indexed | 2024-04-10T22:59:09Z |
| format | Article |
| id | doaj.art-780490df861446fbb2b17dfaf51ca12a |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-10T22:59:09Z |
| publishDate | 2023-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-780490df861446fbb2b17dfaf51ca12a2023-01-14T04:26:12ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-02-01158114211Pyridoxamine prevents increased atherosclerosis by intermittent methylglyoxal spikes in the aortic arches of ApoE-/- miceNordin M.J. Hanssen0Chris Tikellis1Raelene J. Pickering2Dragana Dragoljevic3Man Kit Sam Lee4Tomasz Block5Jean LJM Scheijen6Kristiaan Wouters7Toshio Miyata8Mark E. Cooper9Andrew J. Murphy10Merlin C. Thomas11Casper G. Schalkwijk12Amsterdam Diabetes Centrum, Internal and Vascular Medicine, Amsterdam University Medical Centres, location AMC, Amsterdam, the NetherlandsDepartment of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, AustraliaDepartment of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, AustraliaDept. of leukocyte biology and haematopoiesis, Baker Heart and Diabetes Institute, Melbourne, AustraliaDept. of leukocyte biology and haematopoiesis, Baker Heart and Diabetes Institute, Melbourne, AustraliaDepartment of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, AustraliaDept. of Internal Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands; CARIM School for Cardiovascular Diseases, Maastricht, the NetherlandsDept. of Internal Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands; CARIM School for Cardiovascular Diseases, Maastricht, the NetherlandsDivision of Molecular Medicine and Therapy, Tohoku University Graduate School of Medicine, JapanDepartment of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, AustraliaDept. of leukocyte biology and haematopoiesis, Baker Heart and Diabetes Institute, Melbourne, AustraliaDepartment of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, AustraliaDept. of Internal Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands; CARIM School for Cardiovascular Diseases, Maastricht, the Netherlands; Corresponding author at: Dept. of Internal Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands.Methylglyoxal (MGO) is a reactive glucose metabolite linked to diabetic cardiovascular disease (CVD). MGO levels surge during intermittent hyperglycemia. We hypothesize that these MGO spikes contribute to atherosclerosis, and that pyridoxamine as a MGO quencher prevents this injury. To study this, we intravenously injected normoglycemic 8-week old male C57Bl6 ApoE-/- mice with normal saline (NS, n = 10) or 25 µg MGO for 10 consecutive weeks (MGOiv, n = 11) with or without 1 g/L pyridoxamine (MGOiv+PD, n = 11) in the drinking water. We measured circulating immune cells by flow cytometry. We quantified aortic arch lesion area in aortic roots after Sudan-black staining. We quantified the expression of inflammatory genes in the aorta by qPCR. Intermittent MGO spikes weekly increased atherosclerotic burden in the arch 1.8-fold (NS: 0.9 ± 0.1 vs 1.6 ± 0.2 %), and this was prevented by pyridoxamine (0.8 ± 0.1 %). MGOiv spikes increased circulating neutrophils and monocytes (2-fold relative to NS) and the expression of ICAM (3-fold), RAGE (5-fold), S100A9 (2-fold) and MCP1 (2-fold). All these changes were attenuated by pyridoxamine. This study suggests that MGO spikes damages the vasculature independently of plasma glucose levels. Pyridoxamine and potentially other approaches to reduce MGO may prevent excess cardiovascular risk in diabeteshttp://www.sciencedirect.com/science/article/pii/S0753332222016006MethylglyoxalPyridoxamineAtherosclerosisDiabetesDicarbonyl stress |
| spellingShingle | Nordin M.J. Hanssen Chris Tikellis Raelene J. Pickering Dragana Dragoljevic Man Kit Sam Lee Tomasz Block Jean LJM Scheijen Kristiaan Wouters Toshio Miyata Mark E. Cooper Andrew J. Murphy Merlin C. Thomas Casper G. Schalkwijk Pyridoxamine prevents increased atherosclerosis by intermittent methylglyoxal spikes in the aortic arches of ApoE-/- mice Biomedicine & Pharmacotherapy Methylglyoxal Pyridoxamine Atherosclerosis Diabetes Dicarbonyl stress |
| title | Pyridoxamine prevents increased atherosclerosis by intermittent methylglyoxal spikes in the aortic arches of ApoE-/- mice |
| title_full | Pyridoxamine prevents increased atherosclerosis by intermittent methylglyoxal spikes in the aortic arches of ApoE-/- mice |
| title_fullStr | Pyridoxamine prevents increased atherosclerosis by intermittent methylglyoxal spikes in the aortic arches of ApoE-/- mice |
| title_full_unstemmed | Pyridoxamine prevents increased atherosclerosis by intermittent methylglyoxal spikes in the aortic arches of ApoE-/- mice |
| title_short | Pyridoxamine prevents increased atherosclerosis by intermittent methylglyoxal spikes in the aortic arches of ApoE-/- mice |
| title_sort | pyridoxamine prevents increased atherosclerosis by intermittent methylglyoxal spikes in the aortic arches of apoe mice |
| topic | Methylglyoxal Pyridoxamine Atherosclerosis Diabetes Dicarbonyl stress |
| url | http://www.sciencedirect.com/science/article/pii/S0753332222016006 |
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