Pyridoxamine prevents increased atherosclerosis by intermittent methylglyoxal spikes in the aortic arches of ApoE-/- mice
Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:158 |
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| Enthalten in: |
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie - 158(2023) vom: 09. Feb., Seite 114211 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hanssen, Nordin M J [VerfasserIn] |
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| Links: |
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| Themen: |
3A3U0GI71G |
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| Anmerkungen: |
Date Completed 15.03.2023 Date Revised 15.03.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.biopha.2022.114211 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM354220209 |
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| 520 | |a Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Atherosclerosis | |
| 650 | 4 | |a Diabetes | |
| 650 | 4 | |a Dicarbonyl stress | |
| 650 | 4 | |a Methylglyoxal | |
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| 700 | 1 | |a Dragoljevic, Dragana |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Man Kit Sam |e verfasserin |4 aut | |
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| 700 | 1 | |a Scheijen, Jean Ljm |e verfasserin |4 aut | |
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| 700 | 1 | |a Cooper, Mark E |e verfasserin |4 aut | |
| 700 | 1 | |a Murphy, Andrew J |e verfasserin |4 aut | |
| 700 | 1 | |a Thomas, Merlin C |e verfasserin |4 aut | |
| 700 | 1 | |a Schalkwijk, Casper G |e verfasserin |4 aut | |
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