Red Blood Cell Adenylate Energetics Is Related to Endothelial and Microvascular Function in Long COVID
Adenine nucleotides play a critical role in maintaining essential functions of red blood cells (RBCs), including energy metabolism, redox status, shape fluctuations and RBC-dependent endothelial and microvascular functions. Recently, it has been shown that infection with the severe acute respiratory...
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MDPI AG
2024-03-01
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| Online Access: | https://www.mdpi.com/2227-9059/12/3/554 |
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| author | Marzena Romanowska-Kocejko Agata Jędrzejewska Alicja Braczko Klaudia Stawarska Oliwia Król Marika Frańczak Gabriela Harasim Ryszard T. Smoleński Marcin Hellmann Barbara Kutryb-Zając |
| author_facet | Marzena Romanowska-Kocejko Agata Jędrzejewska Alicja Braczko Klaudia Stawarska Oliwia Król Marika Frańczak Gabriela Harasim Ryszard T. Smoleński Marcin Hellmann Barbara Kutryb-Zając |
| author_sort | Marzena Romanowska-Kocejko |
| collection | DOAJ |
| description | Adenine nucleotides play a critical role in maintaining essential functions of red blood cells (RBCs), including energy metabolism, redox status, shape fluctuations and RBC-dependent endothelial and microvascular functions. Recently, it has been shown that infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) might lead to morphological and metabolic alterations in erythrocytes in both mild and severe cases of coronavirus disease (COVID-19). However, little is known about the effects of COVID-19 on the nucleotide energetics of RBCs nor about the potential contribution of nucleotide metabolism to the long COVID syndrome. This study aimed to analyze the levels of adenine nucleotides in RBCs isolated from patients 12 weeks after mild SARS-CoV-2 infection who suffered from long COVID symptoms and to relate them with the endothelial and microvascular function parameters as well as the rate of peripheral tissue oxygen supply. Although the absolute quantities of adenine nucleotides in RBCs were rather slightly changed in long COVID individuals, many parameters related to the endothelial and microcirculatory function showed significant correlations with RBC adenosine triphosphate (ATP) and total adenine nucleotide (TAN) concentration. A particularly strong relationship was observed between ATP in RBCs and the serum ratio of arginine to asymmetric dimethylarginine—an indicator of endothelial function. Consistently, a positive correlation was also observed between the ATP/ADP ratio and diminished reactive hyperemic response in long COVID patients, assessed by the flow-mediated skin fluorescence (FMSF) technique, which reflected decreased vascular nitric oxide bioavailability. In addition, we have shown that patients after COVID-19 have significantly impaired ischemic response parameters (IR max and IR index), examined by FMSF, which revealed diminished residual bioavailability of oxygen in epidermal keratinocytes after brachial artery occlusion. These ischemic response parameters revealed a strong positive correlation with the RBC ATP/ADP ratio, confirming a key role of RBC bioenergetics in peripheral tissue oxygen supply. Taken together, the outcomes of this study indicate that dysregulation of metabolic processes in erythrocytes with the co-occurring endothelial and microvascular dysfunction is associated with diminished intracellular oxygen delivery, which may partly explain long COVID-specific symptoms such as physical impairment and fatigue. |
| first_indexed | 2024-04-24T18:30:52Z |
| format | Article |
| id | doaj.art-175c96e067894c6c8063887133f193be |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-04-24T18:30:52Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
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| series | Biomedicines |
| spelling | doaj.art-175c96e067894c6c8063887133f193be2024-03-27T13:22:47ZengMDPI AGBiomedicines2227-90592024-03-0112355410.3390/biomedicines12030554Red Blood Cell Adenylate Energetics Is Related to Endothelial and Microvascular Function in Long COVIDMarzena Romanowska-Kocejko0Agata Jędrzejewska1Alicja Braczko2Klaudia Stawarska3Oliwia Król4Marika Frańczak5Gabriela Harasim6Ryszard T. Smoleński7Marcin Hellmann8Barbara Kutryb-Zając9Department of Cardiac Diagnostics, Medical University of Gdansk, 80-210 Gdansk, PolandDepartment of Biochemistry, Medical University of Gdansk, 80-211 Gdansk, PolandDepartment of Biochemistry, Medical University of Gdansk, 80-211 Gdansk, PolandDepartment of Biochemistry, Medical University of Gdansk, 80-211 Gdansk, PolandDepartment of Biochemistry, Medical University of Gdansk, 80-211 Gdansk, PolandDepartment of Biochemistry, Medical University of Gdansk, 80-211 Gdansk, PolandDepartment of Biochemistry, Medical University of Gdansk, 80-211 Gdansk, PolandDepartment of Biochemistry, Medical University of Gdansk, 80-211 Gdansk, PolandDepartment of Cardiac Diagnostics, Medical University of Gdansk, 80-210 Gdansk, PolandDepartment of Biochemistry, Medical University of Gdansk, 80-211 Gdansk, PolandAdenine nucleotides play a critical role in maintaining essential functions of red blood cells (RBCs), including energy metabolism, redox status, shape fluctuations and RBC-dependent endothelial and microvascular functions. Recently, it has been shown that infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) might lead to morphological and metabolic alterations in erythrocytes in both mild and severe cases of coronavirus disease (COVID-19). However, little is known about the effects of COVID-19 on the nucleotide energetics of RBCs nor about the potential contribution of nucleotide metabolism to the long COVID syndrome. This study aimed to analyze the levels of adenine nucleotides in RBCs isolated from patients 12 weeks after mild SARS-CoV-2 infection who suffered from long COVID symptoms and to relate them with the endothelial and microvascular function parameters as well as the rate of peripheral tissue oxygen supply. Although the absolute quantities of adenine nucleotides in RBCs were rather slightly changed in long COVID individuals, many parameters related to the endothelial and microcirculatory function showed significant correlations with RBC adenosine triphosphate (ATP) and total adenine nucleotide (TAN) concentration. A particularly strong relationship was observed between ATP in RBCs and the serum ratio of arginine to asymmetric dimethylarginine—an indicator of endothelial function. Consistently, a positive correlation was also observed between the ATP/ADP ratio and diminished reactive hyperemic response in long COVID patients, assessed by the flow-mediated skin fluorescence (FMSF) technique, which reflected decreased vascular nitric oxide bioavailability. In addition, we have shown that patients after COVID-19 have significantly impaired ischemic response parameters (IR max and IR index), examined by FMSF, which revealed diminished residual bioavailability of oxygen in epidermal keratinocytes after brachial artery occlusion. These ischemic response parameters revealed a strong positive correlation with the RBC ATP/ADP ratio, confirming a key role of RBC bioenergetics in peripheral tissue oxygen supply. Taken together, the outcomes of this study indicate that dysregulation of metabolic processes in erythrocytes with the co-occurring endothelial and microvascular dysfunction is associated with diminished intracellular oxygen delivery, which may partly explain long COVID-specific symptoms such as physical impairment and fatigue.https://www.mdpi.com/2227-9059/12/3/554long COVIDred blood cellsnucleotidesmicrocirculationendothelium |
| spellingShingle | Marzena Romanowska-Kocejko Agata Jędrzejewska Alicja Braczko Klaudia Stawarska Oliwia Król Marika Frańczak Gabriela Harasim Ryszard T. Smoleński Marcin Hellmann Barbara Kutryb-Zając Red Blood Cell Adenylate Energetics Is Related to Endothelial and Microvascular Function in Long COVID Biomedicines long COVID red blood cells nucleotides microcirculation endothelium |
| title | Red Blood Cell Adenylate Energetics Is Related to Endothelial and Microvascular Function in Long COVID |
| title_full | Red Blood Cell Adenylate Energetics Is Related to Endothelial and Microvascular Function in Long COVID |
| title_fullStr | Red Blood Cell Adenylate Energetics Is Related to Endothelial and Microvascular Function in Long COVID |
| title_full_unstemmed | Red Blood Cell Adenylate Energetics Is Related to Endothelial and Microvascular Function in Long COVID |
| title_short | Red Blood Cell Adenylate Energetics Is Related to Endothelial and Microvascular Function in Long COVID |
| title_sort | red blood cell adenylate energetics is related to endothelial and microvascular function in long covid |
| topic | long COVID red blood cells nucleotides microcirculation endothelium |
| url | https://www.mdpi.com/2227-9059/12/3/554 |
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