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In Sickness and in Health: Erythrocyte Responses to Stress and Aging

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (28 February 2021) | Viewed by 47061

Special Issue Editors

Research Lab: Reliability and Quality Control in Laboratory Hematology, Department of Biomedical Sciences, University of West Attica, Agiou Spyridonos 28, Egaleo 12243, Greece
Interests: erythrocyte aging; cell death; eryptosis; removal signaling; stress response; oxidants; disease; cross-talk; extracellular vesicles; omics markers; hemolysis; anemia; hemoglobin defects; storage; transfusion
Department of Biochemistry and Molecular Genetics, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, USA
Interests: blood cells; hypoxia; metabolism; cancer metabolism; trauma; ageing; hemoglobinopathies; transfusion medicine; omics markers
Special Issues, Collections and Topics in MDPI journals
Department of Biology, School of Science, National and Kapodistrian University of Athens (NKUA), Athens, Greece
Interests: erythrocyte aging; cell death; eryptosis; removal signaling; stress response; oxidants; disease; cross-talk; extracellular vesicles; omics markers; hemolysis; anemia; hemoglobin defects; storage; transfusion

Special Issue Information

Dear Colleagues,

Mature red blood cells are the most abundant host cell in our body. Despite their apparent simplicity and unconventional composition (lack of nuclei and organelles) red cells respond to time and external stimuli and reprogram their redox and energy metabolism as a function of biophysical or biochemical triggers, including hypoxia, inflammation, mechanical tension and oxidants. Aging is characterized by modifications in red cell shape, volume, composition, metabolism and several surface molecules, some of which generate senescence signals that trigger erythrophagocytosis. While numerous factors, including chronic and acute oxidative stress, have been shown to contribute to red cell elimination in vitro and in vivo, the etiological triggers of erythrocyte aging and removal from the circulation are still incompletely understood. This holds true not just in the context of physiological aging, but especially in response to pathologies that alter red cell capacity to carry and deliver oxygen (e.g., thalassemia, sickle cell disease) or to counteract oxidant stress (e.g., glucose 6-phosphate dehydrogenase or pyruvate kinase deficiency – the former affecting ~400 million people worldwide). Beyond oxygen delivery, the utmost relevance of red blood cells to regulation of vascular tone, blood coagulation, response to hypoxia and immunomodulation, in addition to pitfalls of iatrogenic interventions (e.g. storage at blood bank) that may harm and modulate them while making them available on demand, set new challenges in the field of transfusion medicine. Reports of red cell modifications in conditions of systemic oxidant stress, dysregulation of oxidative metabolism and iron homeostasis (e.g., ferroptosis) from metabolic syndrome to cancer, from diabetes to neurocognitive impairment and from normal organism aging to inflammatory phenotypes simply reflect the centrality of this cell in our biological universe as a hub cell type of unexpectedly high communicational effectiveness and functional complexity.

This Special Issue focuses on cellular and molecular pathways that work in red cells in response to normal aging and stressful conditions and the translation of those effects in systemic phenotypes of the clinical and sub-clinical spectra. The anticipated contributions will include a selection of research papers, opinions and reviews focused on how red cells change in health and disease, in vivo and in vitro, and on the possible contribution of those readouts to deeper understanding of red cell homeostasis as a key and informative piece of the whole interwired system.

Dr. Anastasios G. Kriebardisu
Prof. Angelo D'Alessandro
Dr. Marianna H. Antonelou
Guest Editors

Keywords

  • erythrocytes
  • removal signaling
  • cell death
  • anemia
  • stress response
  • omics
  • disease
  • extracellular vesicles
  • storage lesion

Published Papers (12 papers)

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Editorial

Jump to: Research, Review

6 pages, 183 KiB  
Editorial
In Sickness and in Health: Erythrocyte Responses to Stress and Aging
by Marianna H. Antonelou, Angelo D’Alessandro and Anastasios G. Kriebardis
Int. J. Mol. Sci. 2022, 23(13), 6957; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23136957 - 23 Jun 2022
Viewed by 1116
Abstract
Mature red blood cells (RBC) are the most abundant host cell in our body [...] Full article
(This article belongs to the Special Issue In Sickness and in Health: Erythrocyte Responses to Stress and Aging)

Research

Jump to: Editorial, Review

11 pages, 1453 KiB  
Article
RRx-001 Increases Erythrocyte Preferential Adhesion to the Tumor Vasculature
by Vinay P. Jani, Robert Asaro, Bryan Oronsky and Pedro Cabrales
Int. J. Mol. Sci. 2021, 22(9), 4713; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094713 - 29 Apr 2021
Cited by 4 | Viewed by 2188
Abstract
Red blood cells (RBCs) serve a variety of functions beyond mere oxygen transport both in health and pathology. Notably, RRx-001, a minimally toxic pleiotropic anticancer agent with macrophage activating and vascular normalization properties currently in Phase III trials, induces modification to RBCs which [...] Read more.
Red blood cells (RBCs) serve a variety of functions beyond mere oxygen transport both in health and pathology. Notably, RRx-001, a minimally toxic pleiotropic anticancer agent with macrophage activating and vascular normalization properties currently in Phase III trials, induces modification to RBCs which could promote vascular adhesion similar to sickle cells. This study assessed whether RBCs exposed to RRx-001 adhere to the tumor microvasculature and whether this adhesion alters tumor viability. We next investigated the biomechanics of RBC adhesion in the context of local inflammatory cytokines after treatment with RRx-001 as a potential mechanism for preferential tumor aggregation. Human HEP-G2 and HT-29 tumor cells were subcutaneously implanted into nu/nu mice and were infused with RRx-001-treated and Technetium-99m (99mTc)-labeled blood. RBC adhesion was quantified in an in vitro human umbilical vein endothelial cell (HUVEC) assay under both normoxic and hypoxic conditions with administration of either lipopolysaccharide (LPS) or Tumor necrosis alpha (TNFα) to mimic the known inflammation in the tumor microenvironment. One hour following administration of 99mTc labeled RBCs treated with 10 mg/kg RRx-001, we observed an approximate 2.0-fold and 1.5-fold increase in 99mTc-labeled RBCs compared to vehicle control in HEPG2 and HT-29 tumor models, respectively. Furthermore, we observed an approximate 40% and 36% decrease in HEP-G2 and HT-29 tumor weight, respectively, following treatment with RRx-001. To quantify RBC adhesive potential, we determined τ50, or the shear stress required for 50% disassociation of RBCs from HUVECs. After administration of TNF-α under normoxia, τ50 was determined to be 4.5 dynes/cm2 (95% CI: 4.3–4.7 dynes/cm2) for RBCs treated with 10 μM RRx-001, which was significantly different (p < 0.05) from τ50 in the absence of treatment. Under hypoxic conditions, the difference of τ50 with (4.8 dynes/cm2; 95% CI: 4.6–5.1 dynes/cm2) and without (2.6 dynes/cm2; 95% CI: 2.4–2.8 dynes/cm2) 10 μM RRx-001 treatment was exacerbated (p = 0.05). In conclusion, we demonstrated that RBCs treated with RRx-001 preferentially aggregate in HEP-G2 and HT-29 tumors, likely due to interactions between RRx-001 and cysteine residues within RBCs. Furthermore, RRx-001 treated RBCs demonstrated increased adhesive potential to endothelial cells upon introduction of TNF-α and hypoxia suggesting that RRx-001 may induce preferential adhesion in the tumor but not in other tissues with endothelial dysfunction due to conditions prevalent in older cancer patients such as heart disease or diabetic vasculopathy. Full article
(This article belongs to the Special Issue In Sickness and in Health: Erythrocyte Responses to Stress and Aging)
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14 pages, 4806 KiB  
Article
Image- and Fluorescence-Based Test Shows Oxidant-Dependent Damages in Red Blood Cells and Enables Screening of Potential Protective Molecules
by Manon Bardyn, Jérôme Allard, David Crettaz, Benjamin Rappaz, Gerardo Turcatti, Jean-Daniel Tissot and Michel Prudent
Int. J. Mol. Sci. 2021, 22(8), 4293; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22084293 - 20 Apr 2021
Cited by 5 | Viewed by 3477
Abstract
An increase of oxygen saturation within blood bags and metabolic dysregulation occur during storage of red blood cells (RBCs). It leads to the gradual exhaustion of RBC antioxidant protective system and, consequently, to a deleterious state of oxidative stress that plays a major [...] Read more.
An increase of oxygen saturation within blood bags and metabolic dysregulation occur during storage of red blood cells (RBCs). It leads to the gradual exhaustion of RBC antioxidant protective system and, consequently, to a deleterious state of oxidative stress that plays a major role in the apparition of the so-called storage lesions. The present study describes the use of a test (called TSOX) based on fluorescence and label-free morphology readouts to simply and quickly evaluate the oxidant and antioxidant properties of various compounds in controlled conditions. Here, TSOX was applied to RBCs treated with four antioxidants (ascorbic acid, uric acid, trolox and resveratrol) and three oxidants (AAPH, diamide and H2O2) at different concentrations. Two complementary readouts were chosen: first, where ROS generation was quantified using DCFH-DA fluorescent probe, and second, based on digital holographic microscopy that measures morphology alterations. All oxidants produced an increase of fluorescence, whereas H2O2 did not visibly impact the RBC morphology. Significant protection was observed in three out of four of the added molecules. Of note, resveratrol induced diamond-shape “Tirocytes”. The assay design was selected to be flexible, as well as compatible with high-throughput screening. In future experiments, the TSOX will serve to screen chemical libraries and probe molecules that could be added to the additive solution for RBCs storage. Full article
(This article belongs to the Special Issue In Sickness and in Health: Erythrocyte Responses to Stress and Aging)
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23 pages, 6509 KiB  
Article
Proteome of Stored RBC Membrane and Vesicles from Heterozygous Beta Thalassemia Donors
by Vassilis L. Tzounakas, Alkmini T. Anastasiadi, Monika Dzieciatkowska, Dimitrios G. Karadimas, Konstantinos Stamoulis, Issidora S. Papassideri, Kirk C. Hansen, Angelo D’Alessandro, Anastasios G. Kriebardis and Marianna H. Antonelou
Int. J. Mol. Sci. 2021, 22(7), 3369; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22073369 - 25 Mar 2021
Cited by 14 | Viewed by 2886
Abstract
Genetic characteristics of blood donors may impact the storability of blood products. Despite higher basal stress, red blood cells (RBCs) from eligible donors that are heterozygous for beta-thalassemia traits (βThal+) possess a differential nitrogen-related metabolism, and cope better with storage stress [...] Read more.
Genetic characteristics of blood donors may impact the storability of blood products. Despite higher basal stress, red blood cells (RBCs) from eligible donors that are heterozygous for beta-thalassemia traits (βThal+) possess a differential nitrogen-related metabolism, and cope better with storage stress compared to the control. Nevertheless, not much is known about how storage impacts the proteome of membrane and extracellular vesicles (EVs) in βThal+. For this purpose, RBC units from twelve βThal+ donors were studied through proteomics, immunoblotting, electron microscopy, and functional ELISA assays, versus units from sex- and aged-matched controls. βThal+ RBCs exhibited less irreversible shape modifications. Their membrane proteome was characterized by different levels of structural, lipid raft, transport, chaperoning, redox, and enzyme components. The most prominent findings include the upregulation of myosin proteoforms, arginase-1, heat shock proteins, and protein kinases, but the downregulation of nitrogen-related transporters. The unique membrane proteome was also mirrored, in part, to that of βThal+ EVs. Network analysis revealed interesting connections of membrane vesiculation with storage and stress hemolysis, along with proteome control modulators of the RBC membrane. Our findings, which are in line with the mild but consistent oxidative stress these cells experience in vivo, provide insight into the physiology and aging of stored βThal+ RBCs. Full article
(This article belongs to the Special Issue In Sickness and in Health: Erythrocyte Responses to Stress and Aging)
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16 pages, 1710 KiB  
Article
Predialysis and Dialysis Therapies Differently Affect Nitric Oxide Synthetic Pathway in Red Blood Cells from Uremic Patients: Focus on Peritoneal Dialysis
by Carola Palmerini, Luca Piscitani, Giuseppina Bologna, Chiara Riganti, Paola Lanuti, Domitilla Mandatori, Lorenzo Di Liberato, Giorgia Di Fulvio, Vittorio Sirolli, Giulia Renda, Caterina Pipino, Marco Marchisio, Mario Bonomini, Assunta Pandolfi and Natalia Di Pietro
Int. J. Mol. Sci. 2021, 22(6), 3049; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22063049 - 17 Mar 2021
Cited by 2 | Viewed by 1846
Abstract
Red blood cells (RBCs) have been found to synthesize and release both nitric oxide (NO) and cyclic guanosine monophosphate (cGMP), contributing to systemic NO bioavailability. These RBC functions resulted impaired in chronic kidney disease (CKD). This study aimed to evaluate whether predialysis (conservative [...] Read more.
Red blood cells (RBCs) have been found to synthesize and release both nitric oxide (NO) and cyclic guanosine monophosphate (cGMP), contributing to systemic NO bioavailability. These RBC functions resulted impaired in chronic kidney disease (CKD). This study aimed to evaluate whether predialysis (conservative therapy, CT) and dialysis (peritoneal dialysis, PD; hemodialysis, HD) therapies used during CKD progression may differently affect NO-synthetic pathway in RBCs. Our data demonstrated that compared to PD, although endothelial-NO-synthase activation was similarly increased, HD and CT were associated to cGMP RBCs accumulation, caused by reduced activity of cGMP membrane transporter (MRP4). In parallel, plasma cGMP levels were increased by both CT and HD and they significantly decreased after hemodialysis, suggesting that this might be caused by reduced cGMP renal clearance. As conceivable, compared to healthy subjects, plasma nitrite levels were significantly reduced by HD and CT but not in patients on PD. Additionally, the increased carotid intima-media thickness (IMT) values did not reach the significance exclusively in patients on PD. Therefore, our results show that PD might better preserve the synthetic NO-pathway in CKD-erythrocytes. Whether this translates into a reduced development of uremic vascular complications requires further investigation. Full article
(This article belongs to the Special Issue In Sickness and in Health: Erythrocyte Responses to Stress and Aging)
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16 pages, 2138 KiB  
Article
An Insight into the Stages of Ion Leakage during Red Blood Cell Storage
by Anna Zimna, Magdalena Kaczmarska, Ewa Szczesny-Malysiak, Aleksandra Wajda, Katarzyna Bulat, Fatih Celal Alcicek, Malgorzata Zygmunt, Tomasz Sacha and Katarzyna Maria Marzec
Int. J. Mol. Sci. 2021, 22(6), 2885; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22062885 - 12 Mar 2021
Cited by 7 | Viewed by 3582
Abstract
Packed red blood cells (pRBCs), the most commonly transfused blood product, are exposed to environmental disruptions during storage in blood banks. In this study, temporal sequence of changes in the ion exchange in pRBCs was analyzed. Standard techniques commonly used in electrolyte measurements [...] Read more.
Packed red blood cells (pRBCs), the most commonly transfused blood product, are exposed to environmental disruptions during storage in blood banks. In this study, temporal sequence of changes in the ion exchange in pRBCs was analyzed. Standard techniques commonly used in electrolyte measurements were implemented. The relationship between ion exchange and red blood cells (RBCs) morphology was assessed with use of atomic force microscopy with reference to morphological parameters. Variations observed in the Na+, K+, Cl, H+, HCO3, and lactate ions concentration show a complete picture of singly-charged ion changes in pRBCs during storage. Correlation between the rate of ion changes and blood group type, regarding the limitations of our research, suggested, that group 0 is the most sensitive to the time-dependent ionic changes. Additionally, the impact of irreversible changes in ion exchange on the RBCs membrane was observed in nanoscale. Results demonstrate that the level of ion leakage that leads to destructive alterations in biochemical and morphological properties of pRBCs depend on the storage timepoint. Full article
(This article belongs to the Special Issue In Sickness and in Health: Erythrocyte Responses to Stress and Aging)
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15 pages, 2237 KiB  
Article
Spectroscopic Signature of Red Blood Cells in a D-Galactose-Induced Accelerated Aging Model
by Aneta Blat, Tetiana Stepanenko, Katarzyna Bulat, Aleksandra Wajda, Jakub Dybas, Tasnim Mohaissen, Fatih Celal Alcicek, Ewa Szczesny-Malysiak, Kamilla Malek, Andrzej Fedorowicz and Katarzyna M. Marzec
Int. J. Mol. Sci. 2021, 22(5), 2660; https://doi.org/10.3390/ijms22052660 - 06 Mar 2021
Cited by 9 | Viewed by 3668
Abstract
This work presents a semi-quantitative spectroscopic approach, including FTIR–ATR and Raman spectroscopies, for the biochemical analysis of red blood cells (RBCs) supported by the biochemical, morphological and rheological reference techniques. This multi-modal approach provided the description of the RBC alterations at the molecular [...] Read more.
This work presents a semi-quantitative spectroscopic approach, including FTIR–ATR and Raman spectroscopies, for the biochemical analysis of red blood cells (RBCs) supported by the biochemical, morphological and rheological reference techniques. This multi-modal approach provided the description of the RBC alterations at the molecular level in a model of accelerated aging induced by administration of D-galactose (D-gal), in comparison to natural aging. Such an approach allowed to conclude that most age-related biochemical RBC membrane changes (a decrease in lipid unsaturation and the level of phospholipids, or an increase in acyl chain shortening) as well as alterations in the morphological parameters and RBC deformability are well reflected in the D-gal model of accelerated aging. Similarly, as in natural aging, a decrease in LDL level in blood plasma and no changes in the fraction of glucose, creatinine, total cholesterol, HDL, iron, or triglycerides were observed during the course of accelerated aging. Contrary to natural aging, the D-gal model led to an increase in cholesterol esters and the fraction of total esterified lipids in RBC membranes, and evoked significant changes in the secondary structure of the membrane proteins. Moreover, a significant decrease in the phosphorous level of blood plasma was specific for the D-gal model. On the other hand, natural aging induced stronger changes in the secondary structures of the proteins of the RBCs’ interior. This work proves that research on the aging mechanism, especially in circulation-related diseases, should employ the D-gal model with caution. Nonetheless, the D-gal model enables to imitate age-related rheological alterations in RBCs, although they are partially derived from different changes observed in the RBC membrane at the molecular level. Full article
(This article belongs to the Special Issue In Sickness and in Health: Erythrocyte Responses to Stress and Aging)
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21 pages, 2946 KiB  
Article
Acute Cycling Exercise Induces Changes in Red Blood Cell Deformability and Membrane Lipid Remodeling
by Travis Nemkov, Sarah C. Skinner, Elie Nader, Davide Stefanoni, Mélanie Robert, Francesca Cendali, Emeric Stauffer, Agnes Cibiel, Camille Boisson, Philippe Connes and Angelo D’Alessandro
Int. J. Mol. Sci. 2021, 22(2), 896; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22020896 - 18 Jan 2021
Cited by 40 | Viewed by 3440
Abstract
Here we describe the effects of a controlled, 30 min, high-intensity cycling test on blood rheology and the metabolic profiles of red blood cells (RBCs) and plasma from well-trained males. RBCs demonstrated decreased deformability and trended toward increased generation of microparticles after the [...] Read more.
Here we describe the effects of a controlled, 30 min, high-intensity cycling test on blood rheology and the metabolic profiles of red blood cells (RBCs) and plasma from well-trained males. RBCs demonstrated decreased deformability and trended toward increased generation of microparticles after the test. Meanwhile, metabolomics and lipidomics highlighted oxidative stress and activation of membrane lipid remodeling mechanisms in order to cope with altered properties of circulation resulting from physical exertion during the cycling test. Of note, intermediates from coenzyme A (CoA) synthesis for conjugation to fatty acyl chains, in parallel with reversible conversion of carnitine and acylcarnitines, emerged as metabolites that significantly correlate with RBC deformability and the generation of microparticles during exercise. Taken together, we propose that RBC membrane remodeling and repair plays an active role in the physiologic response to exercise by altering RBC properties. Full article
(This article belongs to the Special Issue In Sickness and in Health: Erythrocyte Responses to Stress and Aging)
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12 pages, 1043 KiB  
Article
Impact of Trail Running Races on Blood Viscosity and Its Determinants: Effects of Distance
by Mélanie Robert, Emeric Stauffer, Elie Nader, Sarah Skinner, Camille Boisson, Agnes Cibiel, Léonard Feasson, Céline Renoux, Paul Robach, Philippe Joly, Guillaume Y. Millet and Philippe Connes
Int. J. Mol. Sci. 2020, 21(22), 8531; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21228531 - 12 Nov 2020
Cited by 8 | Viewed by 4570
Abstract
Blood rheology is a key determinant of tissue perfusion at rest and during exercise. The present study investigated the effects of race distance on hematological, blood rheological, and red blood cell (RBC) senescence parameters. Eleven runners participated in the Martigny–Combes à Chamonix 40 [...] Read more.
Blood rheology is a key determinant of tissue perfusion at rest and during exercise. The present study investigated the effects of race distance on hematological, blood rheological, and red blood cell (RBC) senescence parameters. Eleven runners participated in the Martigny–Combes à Chamonix 40 km race (MCC, elevation gain: 2300 m) and 12 others in the Ultra-Trail du Mont Blanc (UTMB, 171 km, elevation gain: 10,000 m). Blood samples were collected before and after the races. After the UTMB, the percentage of RBC phosphatidylserine (PS) exposure was not affected while RBC CD235a levels decreased and RBC-derived microparticles increased. In contrast, after the MCC, RBC PS exposure increased, while RBC CD235a and RBC-derived microparticles levels were not affected. The free hemoglobin and hemolysis rate did not change during the races. RBC aggregation and blood viscosity at moderate shear rates increased after the MCC. RBC deformability, blood viscosity at a high shear rate, and hematocrit decreased after the UTMB but not after the MCC. Our results indicate that blood rheology behavior is different between a 40 km and a 171 km mountain race. The low blood viscosity after the ultra-marathon might facilitate blood flow to the muscles and optimize aerobic performance. Full article
(This article belongs to the Special Issue In Sickness and in Health: Erythrocyte Responses to Stress and Aging)
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Review

Jump to: Editorial, Research

30 pages, 4264 KiB  
Review
Erythrocytes: Central Actors in Multiple Scenes of Atherosclerosis
by Chloé Turpin, Aurélie Catan, Olivier Meilhac, Emmanuel Bourdon, François Canonne-Hergaux and Philippe Rondeau
Int. J. Mol. Sci. 2021, 22(11), 5843; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22115843 - 29 May 2021
Cited by 23 | Viewed by 5627
Abstract
The development and progression of atherosclerosis (ATH) involves lipid accumulation, oxidative stress and both vascular and blood cell dysfunction. Erythrocytes, the main circulating cells in the body, exert determinant roles in the gas transport between tissues. Erythrocytes have long been considered as simple [...] Read more.
The development and progression of atherosclerosis (ATH) involves lipid accumulation, oxidative stress and both vascular and blood cell dysfunction. Erythrocytes, the main circulating cells in the body, exert determinant roles in the gas transport between tissues. Erythrocytes have long been considered as simple bystanders in cardiovascular diseases, including ATH. This review highlights recent knowledge concerning the role of erythrocytes being more than just passive gas carriers, as potent contributors to atherosclerotic plaque progression. Erythrocyte physiology and ATH pathology is first described. Then, a specific chapter delineates the numerous links between erythrocytes and atherogenesis. In particular, we discuss the impact of extravasated erythrocytes in plaque iron homeostasis with potential pathological consequences. Hyperglycaemia is recognised as a significant aggravating contributor to the development of ATH. Then, a special focus is made on glycoxidative modifications of erythrocytes and their role in ATH. This chapter includes recent data proposing glycoxidised erythrocytes as putative contributors to enhanced atherothrombosis in diabetic patients. Full article
(This article belongs to the Special Issue In Sickness and in Health: Erythrocyte Responses to Stress and Aging)
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29 pages, 848 KiB  
Review
Current Understanding of the Relationship between Blood Donor Variability and Blood Component Quality
by Narges Hadjesfandiari, Mona Khorshidfar and Dana V. Devine
Int. J. Mol. Sci. 2021, 22(8), 3943; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22083943 - 11 Apr 2021
Cited by 5 | Viewed by 5440
Abstract
While differences among donors has long challenged meeting quality standards for the production of blood components for transfusion, only recently has the molecular basis for many of these differences become understood. This review article will examine our current understanding of the molecular differences [...] Read more.
While differences among donors has long challenged meeting quality standards for the production of blood components for transfusion, only recently has the molecular basis for many of these differences become understood. This review article will examine our current understanding of the molecular differences that impact the quality of red blood cells (RBC), platelets, and plasma components. Factors affecting RBC quality include cytoskeletal elements and membrane proteins associated with the oxidative response as well as known enzyme polymorphisms and hemoglobin variants. Donor age and health status may also be important. Platelet quality is impacted by variables that are less well understood, but that include platelet storage sensitive metabolic parameters, responsiveness to agonists accumulating in storage containers and factors affecting the maintenance of pH. An increased understanding of these variables can be used to improve the quality of blood components for transfusion by using donor management algorithms based on a donors individual molecular and genetic profile. Full article
(This article belongs to the Special Issue In Sickness and in Health: Erythrocyte Responses to Stress and Aging)
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24 pages, 2788 KiB  
Review
Extracellular Vesicles from Red Blood Cells and Their Evolving Roles in Health, Coagulopathy and Therapy
by Kiruphagaran Thangaraju, Sabari Nath Neerukonda, Upendra Katneni and Paul W. Buehler
Int. J. Mol. Sci. 2021, 22(1), 153; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010153 - 25 Dec 2020
Cited by 77 | Viewed by 7451
Abstract
Red blood cells (RBCs) release extracellular vesicles (EVs) including both endosome-derived exosomes and plasma-membrane-derived microvesicles (MVs). RBC-derived EVs (RBCEVs) are secreted during erythropoiesis, physiological cellular aging, disease conditions, and in response to environmental stressors. RBCEVs are enriched in various bioactive molecules that facilitate [...] Read more.
Red blood cells (RBCs) release extracellular vesicles (EVs) including both endosome-derived exosomes and plasma-membrane-derived microvesicles (MVs). RBC-derived EVs (RBCEVs) are secreted during erythropoiesis, physiological cellular aging, disease conditions, and in response to environmental stressors. RBCEVs are enriched in various bioactive molecules that facilitate cell to cell communication and can act as markers of disease. RBCEVs contribute towards physiological adaptive responses to hypoxia as well as pathophysiological progression of diabetes and genetic non-malignant hematologic disease. Moreover, a considerable number of studies focus on the role of EVs from stored RBCs and have evaluated post transfusion consequences associated with their exposure. Interestingly, RBCEVs are important contributors toward coagulopathy in hematological disorders, thus representing a unique evolving area of study that can provide insights into molecular mechanisms that contribute toward dysregulated hemostasis associated with several disease conditions. Relevant work to this point provides a foundation on which to build further studies focused on unraveling the potential roles of RBCEVs in health and disease. In this review, we provide an analysis and summary of RBCEVs biogenesis, composition, and their biological function with a special emphasis on RBCEV pathophysiological contribution to coagulopathy. Further, we consider potential therapeutic applications of RBCEVs. Full article
(This article belongs to the Special Issue In Sickness and in Health: Erythrocyte Responses to Stress and Aging)
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