Abstract
Angiotensin II (Ang II) regulates blood volume and stimulates erythropoiesis through AT1 (ATR1) and AT2 (ATR2) receptors, found in multiple tissues, including erythrocytes. Sickle cell disease (SCD) patients present altered Ang II levels. Hemoglobin S polymerization, deformability and phosphatidylserine translocation are important features of mature erythrocytes, therefore, our hypothesis is Ang II affects these parameters and, if it does, what would be the influence of AT1R and AT2R on these effects. A polymerization assay (PA), deformability, and annexin V binding were performed in SCD erythrocytes samples adding Ang II, ATR1 antagonist (losartan or eprosartan), and ATR2 antagonist (PD123319). Through the PA test, we observed a dose-dependent polymerization inhibition effect when comparing Ang II to control. Losartan did not affect the level or the rate of Ang II inhibition, while PD123319 showed an increased level of protection against polymerization, and eprosartan brought levels back to control. Ang II was able to reduce the translocation of phosphatidylserine from the inner to the outer leaflet, a marker of eryptosis, in the presence of PD123319. Also, ATR1 showed a positive effect increasing deformability. Our data shows that ATR1 is important for maintenance of erythrocyte physiological function in SCD and for prolonging its life.
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The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Acknowledgements
We thank FAPERJ, FUNEMAC, CAPEs, and CNPq for financial support.
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This study was supported by Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (ARC-2019 E-26/010.002689/2019) (JCNE-FAPERJ, E-26/201.520/2014; Edital Sediadas-FAPERJ, E-26/010.000175/2016), Conselho Nacional de Desenvolvimento Científico (CNPq) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES/Ciências sem Fronteiras/PVE/88881.062218/2014-0), who supported the scholarship. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Guimarães-Nobre, C.C., Mendonça-Reis, E., Teixeira-Alves, L.R. et al. ATR1 Angiotensin II Receptor Reduces Hemoglobin S Polymerization, Phosphatidylserine Exposure, and Increases Deformability of Sickle Cell Disease Erythrocytes. Cell Biochem Biophys 80, 711–721 (2022). https://doi.org/10.1007/s12013-022-01096-y
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DOI: https://doi.org/10.1007/s12013-022-01096-y