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Dynamic thiol/disulphide homeostasis in patients with hypertrophic cardiomyopathy

Dynamische Thiol/Disulfid-Homöostase bei Patienten mit hypertropher Kardiomyopathie

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Abstract

Background

In addition to the genetic complexity of hypertrophic cardiomyopathy (HCM), there must be other disease-modifying factors that contribute to its highly variable clinical and phenotypic expression. The authors aimed to investigate serum thiol/disulphide homeostasis as a proxy for oxidative stress using a novel automated assay in patients with HCM.

Methods

This cross-sectional study was conducted on 119 patients with HCM and 52 without HCM. The methods used to measure dynamic thiol/disulphide homeostasis as calorimetric and duplex quantities were developed in 2014.

Results

Median serum native thiol levels were significantly lower in patients with HCM than in those without (312.5 μmol/L [285–370 μmol/L] vs 421 μmol/L [349–469.5 μmol/L]; p < 0.001). Serum total thiol levels and disulphide levels were considerably lower than those in the control group ([844.68 ± 195.99 μmol/L vs 1158.92 ± 243.97 μmol/L; p < 0.001], [259.13 ± 65.66 μmol/L vs 375.02 ± 79.99 μmol/L; p < 0.001], respectively). Serum disulphide/native thiol ratios and disulphide/total thiol ratios were significantly lower in HCM patients than in controls (0.80 ± 0.09 vs 0.92 ± 0.05; p < 0.001 and 0.31 [0.30–0.32] vs 0.32 [0.32–0.33]; p < 0.001). Finally, reduced thiol ratios were higher and oxidized thiol ratios were significantly lower in patients with HCM than in controls.

Conclusions

Despite the fact that antioxidant capacity was impaired, the extracellular environment remained in a reducing state by keeping serum disulphide/native thiol ratios low. Therefore, the authors speculate that HCM may behave similarly to tumours with respect to serum thiol-disulphide levels.

Zusammenfassung

Hintergrund

Neben der genetischen Komplexität der hypertrophen Kardiomyopathie (HCM) muss es weitere krankheitsmodifizierende Faktoren geben, die zur hoch variablen klinischen und phänotypischen Ausprägung der Erkrankung beitragen. Ziel der vorliegenden Arbeit war es, die Thiol/Disulfid-Homöostase im Serum als einen Surrogatparameter für oxidativen Stress bei Patienten mit HCM zu untersuchen; dabei kam ein neuartiger automatisierter Assay zum Einsatz.

Methoden

In diese Querschnittstudie wurden 119 Patienten mit und 52 Patienten ohne HCM eingeschlossen. Die Verfahren zur Messung der dynamischen Thiol/Disulfid-Homöostase als kalorimetrische und Duplex-Mengen wurden 2014 entwickelt.

Ergebnisse

Die medianen Serumkonzentrationen von nativem Thiol waren bei Patienten mit HCM signifikant niedriger als bei Patienten ohne die Erkrankung: 312,5 μmol/l (285–370 μmol/l) vs. 421 μmol/l (349–469,5 μmol/l); p < 0,001. Die Gesamtthiol- und Disulfidkonzentrationen im Serum waren erheblich niedriger als in der Kontrollgruppe: 844,68 ± 195,99 μmol/l vs. 1158,92 ± 243,97 μmol/l; p < 0,001; 259,13 ± 65,66 μmol/l vs. 375,02 ± 79,99 μmol/l; p < 0,001. Das Verhältnis von Disulfiden zu nativem Thiol und von Disulfiden zu Gesamtthiol war bei Patienten mit HCM signifikant niedriger als in der Kontrollgruppe: 0,80 ± 0,09 vs. 0,92 ± 0,05; p < 0,001; 0,31 (0,30–0,32) vs. 0,32 (0,32–0,33); p < 0,001. Zudem war das Verhältnis reduzierter Thiole bei Patienten mit HCM höher als in der Kontrollgruppe, das Verhältnis oxidierter Thiole dagegen niedriger.

Schlussfolgerungen

Obwohl die antioxidative Kapazität beeinträchtigt war, blieb das extrazelluläre Milieu in einem reduzierten Zustand, indem die Verhältnisse von Disulfiden zu nativem Thiol im Serum niedrig gehalten wurden. Daher vermuten wir, dass sich die HCM in Bezug auf Thiol‑/Disulfidspiegel im Serum ähnlich verhält wie Tumoren.

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Acknowledgements

The authors would like to thank Professor Dr. Ramazan Akdemir, the dean of the Medicine Faculty of Sakarya University, for all his contributions to this research.

Funding

This research was supported by a Sakarya University Project Support Fund.

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Authors and Affiliations

  1. Department of Cardiology, University of Health Sciences, Kartal Kosuyolu Education and Research Hospital, Denizer street, 34865, Kartal/Istanbul, Turkey

    Munevver Sari MD, Bahadir Omar MD, Elnur Alizade MD, Abdulkadir Uslu MD & Selcuk Pala MD

  2. Department of Biostatistics, Faculty of Medicine, Sakarya University, 54290, Sakarya, Turkey

    Unal Erkorkmaz MD

  3. Department of Biochemistry, Faculty of Medicine, Sakarya University, 54290, Sakarya, Turkey

    Hayrullah Yazar MD

  4. Department of Cardiology, Sakarya University Education and Research Hospital, 54290, Sakarya, Turkey

    Ibrahim Kocayigit MD & M. N. Murat Aksoy MD

  5. Department of Pathology, Sakarya University Education and Research Hospital, 54290, Sakarya, Turkey

    Gozde Cakirsoy Cakar MD

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  1. Munevver Sari MD
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  2. Unal Erkorkmaz MD
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Correspondence to Munevver Sari MD.

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Conflict of interest

M. Sari, U. Erkorkmaz, H. Yazar, I. Kocayigit, B. Omar, E. Alizade, M.N.M. Aksoy, A. Uslu, G.C. Cakar and S. Pala declare that they have no competing interests.

For this article no studies with human participants or animals were performed by any of the authors. All studies performed were in accordance with the ethical standards indicated in each case.

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Sari, M., Erkorkmaz, U., Yazar, H. et al. Dynamic thiol/disulphide homeostasis in patients with hypertrophic cardiomyopathy. Herz 46, 164–171 (2021). https://doi.org/10.1007/s00059-019-04853-7

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