The Putative Role of Methylglyoxal in Arterial Stiffening: A Review

Heart Lung Circ. 2021 Nov;30(11):1681-1693. doi: 10.1016/j.hlc.2021.06.527. Epub 2021 Aug 12.


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.

Keywords: Advanced glycation endproduct; Cross-linking; Dicarbonyls; Distensibility; Pulse wave velocity; Vascular stiffness.

Publication types

  • Review

MeSH terms

  • Extracellular Matrix
  • Pyruvaldehyde*
  • Vascular Stiffness*


  • Pyruvaldehyde