Advanced glycation end products (AGEs) and cardiovascular dysfunction: focus on high molecular weight AGEs

Abstract

Advanced glycation end products (AGEs) are a group of proteins and lipids becoming glycated and oxidized after persistent contact with reducing sugars or short-chain aldehydes with amino group and/or high degree of oxidative stress. The accumulation of AGEs in the body is a natural process that occurs with senescence, when the turnover rate of proteins is reduced. However, increased circulating AGEs have been described to arise at early lifetime and are associated with adverse outcome and survival, in particular in settings of cardiovascular diseases. AGEs contribute to the development of cardiac dysfunction by two major mechanisms: cross-linking of proteins or binding to their cell surface receptor. Recently, growing evidence shows that high-molecular weight AGEs (HMW-AGEs) might be as important as the characterized low-molecular weight AGEs (LMW-AGEs). Here, we point out the targets of AGEs in the heart and the mechanisms that lead to heart failure with focus on the difference between LMW-AGEs and the less characterized HMW-AGEs. As such, this review is a compilation of relevant papers in the form of a useful resource tool for researchers who want to further investigate the role of HMW-AGEs on cardiac disorders and need a solid base to start on this specific topic.

Impaired calcium homeostasis via advanced glycation end products promotes apoptosis through endoplasmic reticulum stress in human nucleus pulposus cells and exacerbates intervertebral disc degeneration in rats

“…Advanced glycation end products are a heterogeneous class of compounds formed by the nonenzymatic glycation of proteins (i.e., the Maillard reaction), which accumulate in various tissues, including the heart , kidney , brain , joints , and IVD , concomitant with senescence, especially in diabetic individuals. Increasing evidence indicates that AGEs exacerbate disease progression through two potent mechanisms: (a) cross‐linking and modification of ECM structural proteins, such as collagen, leading to altered function and mechanical properties; and/or (b) binding to the AGEs receptor to activate multiple downstream signaling pathways, such as those associated with reactive oxygen species and nuclear factor‐κB .…”

Acute exposure to glycated proteins reduces cardiomyocyte contractile capacity

“…These effects have been attributed mainly to indirect mechanisms, such as enhanced coronary artery disease, inflammation and increased fibrosis, rather than to a direct effect on cardiomyocyte function, and were shown to be mediated through activation of the receptor for advanced glycation end products (RAGE) (Bodiga, Eda, & Bodiga, ). However, our Western diet is a large exogenous source of high molecular weight AGEs (HMW‐AGEs), which are known to be better correlated with complications of type 2 diabetes compared with the well‐characterized LMW‐AGEs (Deluyker, Evens, & Bito, ; Penfold et al., ). Due to their substantial difference in structure, their effects on cardiac function are likely to differ, but to date, data are sparse.…”

Role of the Soluble Receptor for Advanced Glycation End Products (sRAGE) as a Prognostic Factor for Mortality in Hemodialysis and Peritoneal Dialysis Patients

“…AGEs increase in conditions of hyperglycemia, oxidative stress, and uremia and in turn promote inflammation, reactive oxygen/nitrogen species production, apoptosis, and metabolic dysfunctions. In this way, AGEs may accelerate CVD onset and progression [ 3 – 5 ].…”