TY - JOUR
T1 - The Putative Role of Methylglyoxal in Arterial Stiffening
T2 - A Review
AU - van der Bruggen, Myrthe M
AU - Spronck, Bart
AU - Delhaas, Tammo
AU - Reesink, Koen D
AU - Schalkwijk, Casper G
N1 - Funding Information:
BS was supported by the European Union’s Horizon 2020 research and innovation program (No 793805 ).
Funding Information:
BS was supported by the European Union's Horizon 2020 research and innovation program (No 793805).
Publisher Copyright:
© 2021 The Authors
PY - 2021/11
Y1 - 2021/11
N2 - 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: 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: 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.
AB - 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: 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: 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.
KW - Extracellular Matrix
KW - Pyruvaldehyde
KW - Vascular Stiffness
KW - SERUM CARBOXYMETHYL-LYSINE
KW - PULSE-WAVE VELOCITY
KW - AORTIC STIFFNESS
KW - Vascular stiffness
KW - VASCULAR SMOOTH-MUSCLE
KW - RAT MODEL
KW - Distensibility
KW - Cross-linking
KW - VENTRICULAR PROPERTIES
KW - Advanced glycation endproduct
KW - Dicarbonyls
KW - Pulse wave velocity
KW - CARDIOVASCULAR-DISEASE
KW - SKIN AUTOFLUORESCENCE
KW - CROSS-LINK BREAKER
KW - GLYCATION END-PRODUCTS
U2 - 10.1016/j.hlc.2021.06.527
DO - 10.1016/j.hlc.2021.06.527
M3 - (Systematic) Review article
C2 - 34393049
SN - 1443-9506
VL - 30
SP - 1681
EP - 1693
JO - Heart Lung and Circulation
JF - Heart Lung and Circulation
IS - 11
ER -