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. 2025 Jul 18;14(7):888.
doi: 10.3390/antiox14070888.

The Influence of Diabetes Mellitus and Kidney Dysfunction on Oxidative Stress, a Reflection of the Multisystem Interactions in Aortic Stenosis

Laura Mourino-Alvarez  1   2 , Inés Perales-Sánchez  1   2 , Germán Hernández-Fernández  1   2 , Gabriel Blanco-López  1   2 , Emilio Blanco-López  2   3 , Rocío Eiros  4 , Cristian Herrera-Flores  4 , Miryam González-Cebrian  4 , Teresa Tejerina  5 , Jesús Piqueras-Flores  6   7 , Pedro Luis Sánchez  4 , Luis F López-Almodóvar  8 , Luis R Padial  9 , Maria G Barderas  1   2
Affiliations

The Influence of Diabetes Mellitus and Kidney Dysfunction on Oxidative Stress, a Reflection of the Multisystem Interactions in Aortic Stenosis

Laura Mourino-Alvarez et al. Antioxidants (Basel). .

Abstract

Progression of aortic stenosis (AS) is aggravated by type 2 Diabetes Mellitus (T2DM) and kidney dysfunction (KD). Oxidative stress is one of the main mechanisms that triggers AS and is also disturbed among subjects with T2DM and KD. Consequently, we studied the redox homeostasis in four groups of patients, also classifying each patient based on their kidney function: control subjects, T2DM, AS, and AS+T2DM. Free reduced thiols in plasma were analyzed using a colorimetric assay, and the redox state of human serum albumin (HSA) was assessed by immunodetection and PEG-PCMal labeling. Lower levels of thiols were evident in patients with AS and AS+T2DM, while reduced and mildly oxidized HSA was more abundant in T2DM and AS+T2DM patients, reflecting less protection against oxidation. Moreover, the thiol levels decreased as KD increased in patients with AS and AS+T2DM. Differences also exist in reduced and mildly oxidized HSA between patients with normal and severely impaired kidney function, whereas AS patients with severe KD had more strongly oxidized HSA. Our results confirm an imbalance in oxidative stress associated with AS that is aggravated by the coexistence of T2DM and KD. Moreover, T2DM treatment might mitigate this dysfunction, opening the door to new therapeutic approaches for these patients.

Keywords: albumin; aortic stenosis; diabetes mellitus; kidney dysfunction; oxidative stress; thiols.

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Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Free reduced thiol levels in plasma samples. (A) Levels of free reduced thiols in plasma from the 4 study groups. (B) Levels of free reduced thiols in plasma according to the eGFR. * p-value < 0.05.
Figure 2
Figure 2
The redox state of human serum albumin in plasma samples. (A) Western blot of HSA labeled with the Sulfobiotics reagent detected in three different redox states. (B) Relative quantification of the three redox states of albumin: HSAred, HSAox1, and HSAox2. (C–E) The results expressed according to the eGFR of HSAred (C), HSAox1 (D), and HSAox2 (E). (F–H) Correlation between the thiol levels and the different HSA redox states: HSAred (F), HSAox1 (G), and HSAox2 (H). * p-value < 0.05.
Figure 3
Figure 3
Bubble chart of the correlations between the parameters studied (thiols, HSAred, HSAox1, and HSAox2, and eGFR) in the different patient groups: controls (C), patients with DM (DM), patients with AS (AS), and patients with AS and DM (AS+DM). The area is proportional to the p-value, which is also shown, while the color is indicative of the R2 coefficient. * p-value < 0.05.
Figure 4
Figure 4
Summary of the main findings and conclusions of this work.
See this image and copyright information in PMC

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