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ORIGINAL RESEARCH article

Front. Physiol.
Sec. Red Blood Cell Physiology
Volume 15 - 2024 | doi: 10.3389/fphys.2024.1497346

Hypoxia Induces Robust ATP Release from Erythrocytes in ApoE-LDLR Double-deficient Mice

Provisionally accepted
Fatih Celal Alcicek Fatih Celal Alcicek 1,2*Jakub Dybas Jakub Dybas 2Katarzyna Bulat Katarzyna Bulat 3*Tasnim Mohaissen Tasnim Mohaissen 2*Ewa Szczęsny-Małysiak Ewa Szczęsny-Małysiak 2Magdalena Franczyk-Zarow Magdalena Franczyk-Zarow 4*Katarzyna M. Marzec Katarzyna M. Marzec 3*
  • 1 Goethe University Frankfurt, Institute for Cardiovascular Physiology, Frankfurt, Germany
  • 2 Jagiellonian Centre for Experimental Therapeutics, Jagiellonian University, Kraków, Lesser Poland, Poland
  • 3 Faculty of Physics and Applied Computer Science, AGH University of Science and Technology, Krakow, Lesser Poland, Poland
  • 4 Department of Human Nutrition and Dietetics, Faculty of Food Technology, University of Agriculture in Krakow, Krakow, Poland

The final, formatted version of the article will be published soon.

    Red blood cells (RBCs) play a role in the regulation of vascular tone via release of adenosine triphosphate (ATP) into the vasculature in response to various stimuli. Interestingly, ApoE/LDLR double-deficient (ApoE/LDLR -/-) mice, a murine model of atherosclerosis, displays a higher exercise capacity compared to the age-matched controls. However, it is not known whether increased exercise capacity in ApoE/LDLR -/-mice is linked to the altered ATP release from RBCs. In this work, we characterized the ATP release feature of RBCs from ApoE/LDLR -/-mice by exposing them to various stimuli in vitro. The results are linked to the previously reported mechanical and biochemical alterations in RBCs.3V-induced ATP release from RBCs was at comparable levels for all groups, which indicated that the activity of adenylyl cyclase and the components of upstream signal-transduction pathway were intact. Moreover, hypoxia-and low pH-induced ATP release from RBCs was higher in ApoE/LDLR -/-mice compared to their age-matched controls, a potential contributing factor and a finding in line with the higher exercise capacity. Taken together, augmented hypoxia-induced ATP release from RBCs in ApoE/LDLR -/-mice indicates a possible deterioration in the ATP release pathway. This supports our previous reports on the role of the protein structure alterations of RBC cytosol in hypoxia-induced ATP release from RBCs in ApoE/LDLR -/-mice. Thus, we emphasize that the presented herein results are the first step to future pharmacological modification of pathologically impaired microcirculation.

    Keywords: red blood cells, Hemoglobin, ATP release, hypoxia, Atherosclerosis

    Received: 16 Sep 2024; Accepted: 31 Oct 2024.

    Copyright: © 2024 Alcicek, Dybas, Bulat, Mohaissen, Szczęsny-Małysiak, Franczyk-Zarow and Marzec. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Fatih Celal Alcicek, Goethe University Frankfurt, Institute for Cardiovascular Physiology, Frankfurt, Germany
    Katarzyna Bulat, Faculty of Physics and Applied Computer Science, AGH University of Science and Technology, Krakow, 30-059, Lesser Poland, Poland
    Tasnim Mohaissen, Jagiellonian Centre for Experimental Therapeutics, Jagiellonian University, Kraków, 30-348, Lesser Poland, Poland
    Magdalena Franczyk-Zarow, Department of Human Nutrition and Dietetics, Faculty of Food Technology, University of Agriculture in Krakow, Krakow, 31-120, Poland
    Katarzyna M. Marzec, Faculty of Physics and Applied Computer Science, AGH University of Science and Technology, Krakow, 30-059, Lesser Poland, Poland

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