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Metformin and empagliflozin modulate monoamine oxidase-related oxidative stress and improve vascular function in human mammary arteries

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Abstract

Monoamine oxidases (MAOs), mitochondrial enzymes with two isoforms, A and B, have been recently recognized as significant contributors to oxidative stress in the cardiovascular system. The present study was purported to assess the effect of metformin and empagliflozin on MAO expression, oxidative stress and vascular reactivity in internal mammary arteries harvested from overweight patients with coronary heart disease subjected to bypass grafting. Vascular rings were prepared and acutely incubated (12 h) with high glucose (GLUC, 400 mg/dL) or angiotensin II (AII, 100 nM) and metformin (10 µM) and/or empagliflozin (10 µM) and used for the assessment of MAO expression (qRT-PCR and immune histochemistry), reactive oxygen species (ROS, confocal microscopy and spectrophotometry), and vasomotor function (myograph). Ex vivo stimulation with GLUC or AII increased both MAOs expression, ROS production and impaired relaxation to acetylcholine (ACh) of the vascular rings. All effects were alleviated by incubation with each antidiabetic drug; no cumulative effect was obtained when the drugs were applied together. In conclusion, MAO-A and B are upregulated in mammary arteries after acute stimulation with GLUC and AII. Endothelial dysfunction and oxidative stress were alleviated by either metformin or empagliflozin in both stimulated and non-stimulated vascular samples harvested from overweight cardiac patients.

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The datasets generated and analysed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by the university internal funds awarded to the research centres.

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Authors and Affiliations

  1. Department III Functional Sciences–Pathophysiology, “Victor Babeș” University of Medicine and Pharmacy From Timișoara, Eftimie Murgu Sq. No. 2, 300041, Timișoara, Romania

    Ana Lascu, Claudia Borza, Adrian Sturza & Danina M. Muntean

  2. Centre for Translational Research and Systems Medicine, “Victor Babeș” University of Medicine and Pharmacy From Timișoara, Eftimie Murgu Sq. No. 2, 300041, Timișoara, Romania

    Ana Lascu, Loredana N. Ionică, Darius G. Buriman, Adrian P. Merce, Claudia Borza, Adrian Sturza & Danina M. Muntean

  3. Institute of Cardiovascular Diseases Timișoara, “Victor Babeș” University of Medicine and Pharmacy From Timișoara, Eftimie Murgu Sq. No. 2, 300041, Timișoara, Romania

    Ana Lascu, Adrian P. Merce & Horea B. Feier

  4. Doctoral School Medicine-Pharmacy, “Victor Babeș” University of Medicine and Pharmacy From Timișoara, Eftimie Murgu Sq. No. 2, 300041, Timișoara, Romania

    Loredana N. Ionică & Darius G. Buriman

  5. Department VII Internal Medicine–Diabetes, Nutrition and Metabolic Diseases, “Victor Babeș” University of Medicine and Pharmacy From Timișoara, Eftimie Murgu Sq. No. 2, 300041, Timișoara, Romania

    Loredana Deaconu

  6. Department IX Surgery–Surgical Semiotics I, “Victor Babeș” University of Medicine and Pharmacy From Timișoara, Eftimie Murgu Sq. No. 2, 300041, Timișoara, Romania

    Octavian M. Crețu

  7. Centre for Hepato-Biliary and Pancreatic Surgery, “Victor Babeș” University of Medicine and Pharmacy From Timișoara, Eftimie Murgu Sq. No. 2, 300041, Timișoara, Romania

    Octavian M. Crețu

  8. Department VI Cardiology–Cardiovascular Surgery, “Victor Babeș” University of Medicine and Pharmacy From Timișoara, Eftimie Murgu Sq. No. 2, 300041, Timișoara, Romania

    Horea B. Feier

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  1. Ana Lascu
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  2. Loredana N. Ionică
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  4. Adrian P. Merce
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Contributions

AL: original draft preparation, formal analysis; LNI: investigation, formal analysis; DGB: investigation, methodology; APM: investigation, methodology; LD: visualization; CB: visualization, supervision; OMC: project administration; AS: conceptualization, data curation, writing-review & editing; DMM: conceptualization, writing-review & editing, HBF: visualization, supervision. All authors read and approved the final manuscript.

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Correspondence to Adrian Sturza.

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The authors have no relevant financial or non-financial interests to disclose.

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This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Committee for Research Ethics of „Victor Babeș” University of Medicine and Pharmacy from Timișoara, Romania (No. 04/28.02.2020 and 04p/17/12/2020).

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Lascu, A., Ionică, L.N., Buriman, D.G. et al. Metformin and empagliflozin modulate monoamine oxidase-related oxidative stress and improve vascular function in human mammary arteries. Mol Cell Biochem 478, 1939–1947 (2023). https://doi.org/10.1007/s11010-022-04633-8

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