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Serum levels of autoantibodies against the angiotensin II type I receptor are not associated with serum dicarbonyl or AGE levels in patients with an aldosterone-producing adenoma

Journal of Human Hypertension volume 37, pages 919–924 (2023)Cite this article

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Abstract

Patients with an aldosterone-producing adenoma (APA) carry a higher risk of cardiovascular disease and commonly have high levels of autoantibodies (AT1AA) that may activate the angiotensin II type 1 receptor (AT1R). AT1R activation is linked to an increase of the glucose metabolite methylglyoxal (MGO), a potential precursor of advanced glycation endproducts (AGEs) and driver of vascular inflammation. We investigated whether serum AT1AA levels are associated with serum MGO and AGE levels in APA patients. In a case series of 26 patients with APA we measured levels of dicarbonyls MGO, glyoxal (GO) and 3-deoxyglucosone (3-DG), and dicarbonyl-derived AGEs 5-hydro-5-methylimidazolone (MG-H1), Nε-(carboxyethyl)lysine (CEL) and Nε-(carboxymethyl)lysine (CML) with UPLC-MS/MS. We also measured AT1AA by ELISA. These measurements were repeated 1-month after adrenalectomy in a subset of 14 patients. Panels of inflammation and endothelial function were also measured by immunoassays. Although baseline higher AT1AA levels tended to be correlated with higher baseline serum MGO, GO and 3-DG levels (r = 0.18, p = 0.38; r = 0.20, p = 0.33; r = 0.23, p = 0.26; respectively), these correlations were not statistically significant. We observed no obvious correlations between higher AT1AA levels and protein-bound and free MG-H1, CEL and CML levels, and markers of inflammation and endothelial function. No decrease was observed in any of the dicarbonyls, protein-bound AGE levels and markers of inflammation and endothelial function after adrenalectomy. In patients with APA the serum levels of AT1AA were not significantly correlated with serum dicarbonyls, protein-bound and free AGE levels. Increased signalling of the AT1AA receptor may therefore be unlikely to overtly increase systemic dicarbonyl levels.

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Fig. 1: Association of serum markers of inflammation and endothelial function with AT1AA.
Fig. 2: Association of serum dicarbonyls and AGEs with AT1AA.
Fig. 3: Serum levels of dicarbonyls and AGEs before and after adrenalectomy.

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Data availability

The data generated during this study is within the manuscript. Any additional data is available to researchers on request for purposes of reproducing the results or replicating the procedure by contacting the corresponding author.

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Authors and Affiliations

  1. Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, Netherlands

    M. Piazza, J. L. J. M. Scheijen, M. vd Waarenburg, C. D. A. Stehouwer & C. G. Schalkwijk

  2. Cardiovascular Research Institute Maastricht (CARIM), Maastricht, Netherlands

    M. Piazza, N. M. J. Hanssen, J. L. J. M. Scheijen, M. vd Waarenburg, C. D. A. Stehouwer & C. G. Schalkwijk

  3. Department of Medicine-DIMED University of Padua, Padua, Italy

    M. Piazza, B. Caroccia, T. M. Seccia & G. P. Rossi

  4. Department of Vascular and Internal Medicine, Amsterdam University Medical Center, Amsterdam, Netherlands

    N. M. J. Hanssen

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Contributions

MP and NMJH analysed the data and wrote the manuscript. JLJMS measured dicarbonyls, wrote and edited the manuscript. MvW measured dicarbonyls and edited the manuscript, BC, TMS, CDAS, GPR, edited the manuscript, CGS is the principal investigator of the study, wrote and edited the manuscript.

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Correspondence to C. G. Schalkwijk.

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Piazza, M., Hanssen, N.M.J., Scheijen, J.L.J.M. et al. Serum levels of autoantibodies against the angiotensin II type I receptor are not associated with serum dicarbonyl or AGE levels in patients with an aldosterone-producing adenoma. J Hum Hypertens 37, 919–924 (2023). https://doi.org/10.1038/s41371-022-00773-y

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