The Putative Role of Methylglyoxal in Arterial Stiffening: A Review.
Advanced glycation endproduct
Cross-linking
Dicarbonyls
Distensibility
Pulse wave velocity
Vascular stiffness
Journal
Heart, lung & circulation
ISSN: 1444-2892
Titre abrégé: Heart Lung Circ
Pays: Australia
ID NLM: 100963739
Informations de publication
Date de publication:
Nov 2021
Nov 2021
Historique:
received:
22
03
2021
revised:
28
05
2021
accepted:
01
06
2021
pubmed:
17
8
2021
medline:
6
10
2021
entrez:
16
8
2021
Statut:
ppublish
Résumé
Arterial stiffening is a hallmark of vascular ageing and a consequence of many diseases including diabetes mellitus. Methylglyoxal (MGO), a highly reactive α-dicarbonyl mainly formed during glycolysis, has emerged as a potential contributor to the development of arterial stiffness. MGO reacts with arginine and lysine residues in proteins to form stable advanced glycation endproducts (AGEs). AGEs may contribute to arterial stiffening by increased cross-linking of collagen within the extracellular matrix (ECM), by altering the vascular structure, and by triggering inflammatory and oxidative pathways. Although arterial stiffness is mainly determined by ECM and vascular smooth muscle cell function, the effects of MGO and MGO-derived AGEs on these structures have not been thoroughly reviewed to date. We conducted a PubMed search without filtering for publication date which resulted in 16 experimental and 22 clinical studies eligible for inclusion. Remarkably, none of the experimental and only three of the clinical studies specifically mentioned MGO-derived AGEs. Almost all studies reported an association between arterial stiffness and AGE accumulation in the arterial wall or increased plasma AGEs. Other studies report reduced arterial stiffness in experimental models upon administration of AGE-breakers. No papers published to date directly show an association between MGO or MGO-derived AGEs and arterial stiffening. The relevance of the various underlying mechanisms is not yet clear, which is particularly due to methodological challenges in the detection of MGO and MGO-derived AGEs at the molecular, intra- and pericellular, and structural levels, as well as in challenges in the assessment of intrinsic arterial wall properties at ECM- and tissue levels.
Sections du résumé
BACKGROUND
BACKGROUND
Arterial stiffening is a hallmark of vascular ageing and a consequence of many diseases including diabetes mellitus. Methylglyoxal (MGO), a highly reactive α-dicarbonyl mainly formed during glycolysis, has emerged as a potential contributor to the development of arterial stiffness. MGO reacts with arginine and lysine residues in proteins to form stable advanced glycation endproducts (AGEs). AGEs may contribute to arterial stiffening by increased cross-linking of collagen within the extracellular matrix (ECM), by altering the vascular structure, and by triggering inflammatory and oxidative pathways. Although arterial stiffness is mainly determined by ECM and vascular smooth muscle cell function, the effects of MGO and MGO-derived AGEs on these structures have not been thoroughly reviewed to date.
METHODS AND RESULTS
RESULTS
We conducted a PubMed search without filtering for publication date which resulted in 16 experimental and 22 clinical studies eligible for inclusion. Remarkably, none of the experimental and only three of the clinical studies specifically mentioned MGO-derived AGEs. Almost all studies reported an association between arterial stiffness and AGE accumulation in the arterial wall or increased plasma AGEs. Other studies report reduced arterial stiffness in experimental models upon administration of AGE-breakers.
CONCLUSIONS
CONCLUSIONS
No papers published to date directly show an association between MGO or MGO-derived AGEs and arterial stiffening. The relevance of the various underlying mechanisms is not yet clear, which is particularly due to methodological challenges in the detection of MGO and MGO-derived AGEs at the molecular, intra- and pericellular, and structural levels, as well as in challenges in the assessment of intrinsic arterial wall properties at ECM- and tissue levels.
Identifiants
pubmed: 34393049
pii: S1443-9506(21)01141-0
doi: 10.1016/j.hlc.2021.06.527
pii:
doi:
Substances chimiques
Pyruvaldehyde
722KLD7415
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1681-1693Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.