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The role of advanced glycation end products in vascular aging: which parameter is the most suitable as a biomarker?

Journal of Human Hypertension volume 35, pages 240–249 (2021)Cite this article

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Abstract

Advanced glycation end products (AGEs) are involved in several pathophysiologic processes in vascular diseases, including progressive loss of elasticity of the vessel wall (arterial stiffness). Circulating soluble receptors for AGEs (sRAGE) act as a decoy and counterbalanced the harmful properties of AGEs as the natural protective factor. We compared the role of circulating or skin-deposed AGEs and sRAGE regarding the natural course of arterial stiffening. In a prospective cohort study, we longitudinally followed 536 general population-based subjects (subsample of Czech post-MONICA study). Aortic pulse-wave velocity (PWV) was measured twice (at baseline and after ~8 years of follow-up) using a SphygmoCor device (AtCor Medical Ltd), and the intraindividual change in PWV per year (∆PWV/year) was calculated. Concentrations of sRAGE and carboxymethyl lysine (circulating AGEs) were assessed at the follow-up visit by ELISA, while skin AGEs were measured using the autofluorescence-based device AGE Reader. Using multiple regressions, we found significant association between ∆PWV/year as a dependent variable, and both, sRAGE and skin AGEs as independent ones (each on its own model). However, the closest associations to ∆PWV/year were found for the ratio of these two factors (skin AGEs/sRAGE) [β coeff = 0.0747 (SE 0.0189), p < 0.0001]. In a categorized manner, subjects with skin AGEs/sRAGE ratio ≥ 3.3 showed about twofold higher risk having ΔPWV/year ≥ 0.2 m/s [adjusted odds ratio was 2.09 (95% CI: 1.35–3.22), p = 0.001]. In contrast, neither circulating AGEs nor circulating AGEs/sRAGE showed any significant relation to ΔPWV/year. In conclusion, skin AGEs/sRAGE ratio seems to be a more sensitive biomarker of vascular aging than these single factors themselves or circulation status of AGEs.

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Fig. 1: Study flowchart.
Fig. 2: Individual development in arterial stiffness during follow-up (∆PWV/year) in quartiles of different AGE–RAGE axis parameters [box-and-whisker plots (medians and 95% confidence intervals)].

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Acknowledgements

The study realization was supported by the Health Development Agency of Czech Ministry of Health (project 15-27109), by Charles University Research Fund (PROGRES, project Q39), and by Ministry of Health, Czech Republic—conceptual development of research organization (FNPl, 00669806). We would like to acknowledge the hard work of all investigators and other coworkers (study nurses, laboratory technicians, medical students, …) who participated in the post-MONICA project. Namely, we are grateful to Mrs Martina Peštová for her excellent collaboration, and last but not least, to all study subjects, who voluntarily responded to the very time-consuming clinical examination program.

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Authors and Affiliations

  1. 2nd Department of Internal Medicine, Medical Faculty of Charles University and University Hospital, Pilsen, Czech Republic

    Otto Mayer, Július Gelžinský, Jitka Seidlerová, Markéta Mateřánková, Štěpán Mareš, Veronika Svobodová & Jan Filipovský

  2. Biomedical Center, Medical Faculty of Charles University, Pilsen, Czech Republic

    Otto Mayer, Július Gelžinský, Jitka Seidlerová, Markéta Mateřánková, Štěpán Mareš, Veronika Svobodová & Jan Filipovský

  3. Department of Clinical Biochemistry and Hematology, University Hospital, Pilsen, Czech Republic

    Ladislav Trefil

  4. Centre for Cardiovascular Prevention of the First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic

    Renata Cífková

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  1. Otto Mayer
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Mayer, O., Gelžinský, J., Seidlerová, J. et al. The role of advanced glycation end products in vascular aging: which parameter is the most suitable as a biomarker?. J Hum Hypertens 35, 240–249 (2021). https://doi.org/10.1038/s41371-020-0327-3

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