scholarly journals Fall in the ATP levels in the red blood cells in ApoE-LDLR double-deficient mice model prior to atherosclerosis development

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
F C Alcicek ◽  
T Mohaissen ◽  
K Bulat ◽  
E Szczesny-Malysiak ◽  
J Dybas ◽  
...  

Abstract Background It was previously reported that red blood cells (RBCs) regulate blood flow via RBC-derived ATP [1]. Nevertheless, to the best of our knowledge, no study was performed to characterize possible alterations in RBC ATP levels in ApoE/LDLR−/− mice [2] which constitute a reliable model of human atherosclerosis, displaying distinct erythropathy [3]. Interestingly, young ApoE/LDLR−/− mice display higher exercise capacity and higher O2 carrying capacity of RBCs, as compared to their age-matched control [3,4]. However, it is not known whether increased exerise capacity in ApoE/LDLR−/− mice is linked to altered ATP release from RBCs. It was previously reported that prostacyclin analogs, known atheroprotective agents, which preserve vascular endothelium functions in various diseases [5,6], induce ATP release from human RBCs [1,7]. Purpose To characterize intra- and extra-cellular ATP levels in RBCs isolated from ApoE/LDLR−/− mice in comparison to control mice. Methods All experiments were conducted according to the Guidelines for Animal Care and Treatment of the EU and to the Local Ethical Committee on Animal Testing at our University. For experiments, 8- and 24-week-old C57BL/6 control mice (N=4–6 and N=5–8, respectively) and ApoE/LDLR−/− mice (N=4–7 and N=4–5, respectively) were used. The complete blood count, RBC morphology, biochemistry of blood plasma, RBC deformability, and RBC phosphatidylserine exposure were assessed. The intra- and extra-cellular ATP levels and ATP release from RBCs due to administration of iloprost (100 nM, 1 μM, 10 μm) were studied. Results Intracellular ATP level in RBCs isolated from 8-week-old ApoE/LDLR−/− mice was considerably lower as compared to their age-matched control (7.72±0.77 and 21.23±3.40 pmoles/1x106 RBCs, respectively). In 24-week-old mice, intracellular ATP in RBCs was low not only in ApoE/LDLR−/− mice but also in control mice (8.70±1.30 and 6.27±0.96 pmoles/1x106 RBCs, respectively). Basal extracellular ATP released from RBCs over 30 min incubation was 400 times lower than corresponding intracellular level, and mirrored intracellular ATP levels in all studied groups. Iloprost (100 nM–10 μM) did not produce robust ATP release in any of the studied groups, with only some effects when the highest concentration was used (10 μM). Conclusion(s) Hypercholesterolemia-dependent changes in young ApoE/LDLR−/− mice prior to atherosclerotic plaque development may induce a severe fall in intracellular ATP levels in the RBCs that might be linked to a possible diversion of glycolysis to 2,3-DPG to increase oxygen delivery, and might contribute to the alterations in RBC-dependent regulation of blood flow in ApoE/LDLR−/−. Further studies are required to mechanistically explain these findings. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): 1) National Science Centre, Poland2) the Innovation Incubator 4.0 project funded by the Ministry of Science and Higher Education, Poland

Symmetry ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1020
Author(s):  
Angiolo Farina ◽  
Antonio Fasano ◽  
Fabio Rosso

Blood rheology is a challenging subject owing to the fact that blood is a mixture of a fluid (plasma) and of cells, among which red blood cells make about 50% of the total volume. It is precisely this circumstance that originates the peculiar behavior of blood flow in small vessels (i.e., roughly speaking, vessel with a diameter less than half a millimeter). In this class we find arteriolas, venules, and capillaries. The phenomena taking place in microcirculation are very important in supporting life. Everybody knows the importance of blood filtration in kidneys, but other phenomena, of not less importance, are known only to a small class of physicians. Overviewing such subjects reveals the fascinating complexity of microcirculation.


Author(s):  
Danny Bluestein ◽  
João S. Soares ◽  
Peng Zhang ◽  
Chao Gao ◽  
Seetha Pothapragada ◽  
...  

The coagulation cascade of blood may be initiated by flow induced platelet activation, which prompts clot formation in prosthetic cardiovascular devices and arterial disease processes. While platelet activation may be induced by biochemical agonists, shear stresses arising from pathological flow patterns enhance the propensity of platelets to activate and initiate the intrinsic pathway of coagulation, leading to thrombosis. Upon activation platelets undergo complex biochemical and morphological changes: organelles are centralized, membrane glycoproteins undergo conformational changes, and adhesive pseudopods are extended. Activated platelets polymerize fibrinogen into a fibrin network that enmeshes red blood cells. Activated platelets also cross-talk and aggregate to form thrombi. Current numerical simulations to model this complex process mostly treat blood as a continuum and solve the Navier-Stokes equations governing blood flow, coupled with diffusion-convection-reaction equations. It requires various complex constitutive relations or simplifying assumptions, and is limited to μm level scales. However, molecular mechanisms governing platelet shape change upon activation and their effect on rheological properties can be in the nm level scales. To address this challenge, a multiscale approach which departs from continuum approaches, may offer an effective means to bridge the gap between macroscopic flow and cellular scales. Molecular dynamics (MD) and dissipative particle dynamics (DPD) methods have been employed in recent years to simulate complex processes at the molecular scales, and various viscous fluids at low-to-high Reynolds numbers at mesoscopic scales. Such particle methods possess important properties at the mesoscopic scale: complex fluids with heterogeneous particles can be modeled, allowing the simulation of processes which are otherwise very difficult to solve by continuum approaches. It is becoming a powerful tool for simulating complex blood flow, red blood cells interactions, and platelet-mediated thrombosis involving platelet activation, aggregation, and adhesion.


Author(s):  
Suchita V. Ingale ◽  
Milind P. Ullewar ◽  
Vikas C. Ingale ◽  
Jayshree J. Upadhye

Background: Often, the first test used to diagnose anemia is a complete blood count (CBC). It determines the number, size, volume, and hemoglobin content of red blood cells. Peripheral smear is done for typing of anaemia. Such evaluation is necessary for proper treatment.Methods: A retrospective study was done in 300 anaemic patients at Shakuntala pathology laboratory, Nagpur. Patients were randomly selected including males and females. CBC and peripheral smear were analyzed.Results: Out of total 300 patients evaluated, the prevalence of anaemia was quite significant in females 225 (75%) than males 75 (25%). 66 females (22%) had mild anemia while 129 females (43%) had moderate anemia and 30 females (10%) had severe anaemia 36 males (12%) had mild anaemia, 30 males (10%) had moderate anaemia while 9 males (3%) had severe anaemia. In morphology of red blood cells, normocytic normochromic anaemia was seen in 132 (44%) females and in 45 (15%) of males. Microcytic hypochromic anaemia was seen in 90 (30%) females and 27 (9%) males. Macrocytic anaemia was seen in 3 (1%) females and 3 (1%) males.Conclusions: Prevalence of anaemia is quite high in females than males. Also, the severity of anaemia is more in females than males. So, heath programmes should be directed more towards females since adolescent age.


2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Kelly Thuet ◽  
Elizabeth Bowles ◽  
Meera Sridharan ◽  
Shaquria Adderley ◽  
Randy Sprague ◽  
...  

2015 ◽  
Vol 73 (2) ◽  
Author(s):  
Naveed Abbas ◽  
Dzulkifli Mohamad ◽  
Abdul Hanan Abdullah

The main purpose of this study is to employ the modern technologies and techniques to semi-automate the quantification process of the Red Blood Cells in Microscopic thin blood smear digital images.  The process needs to be more accurate, efficient and universal then the currently practiced methods. The study considers the process to be semi-automated for two reasons, i.e. due to the critical aspect life and due to the diverse nature of the Red Blood Cells in cluster formation. The Methodology of this study involved interactive simple cuts and morphological operations for splitting clusters of Red Blood Cells while counting is carried out through labeling matrix. The Red Blood Cells counting is part of the complete blood count test and is frequently suggested by the Physician to know the number of Red Blood Cells in the patient’s body. The proposed method considers for counting process of the Red Blood Cells first split the clusters and then count the Red Blood Cells. The proposed method achieved an overall True Positive Rate (TPR) of 0.997%, True Negative Rate (TNR) of 0.00265%, accuracy of 0.998% and average error rate of 0.001375% tested on 50 images, data set also on the same number of images linear correlation coefficient R2 is 0.997 between manual and semi-automatic counting of Red Blood Cells.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1585-1585
Author(s):  
John R. Pawloski ◽  
Timothy J. McMahon ◽  
Greg Ahearne ◽  
Claude A. Piantadosi ◽  
David J. Singel ◽  
...  

Abstract Physiological O2 gradients are principal regulators of blood flow in the microcirculation: position-to-position changes in hemoglobin (Hb) O2 saturation are coupled to regulated vasodilation (“hypoxic vasodilation”). The mechanism by which graded changes in O2 content of blood evoke this response has been a great challenge to understand. A new role for red blood cells (RBCs) in hypoxic dilation of blood vessels and inhibition of platelet activation involving release of nitric oxide (NO) bioactivity is described. We show that NO groups can be transferred within hemoglobin (Hb) from hemes to highly-conserved cysteine thiols (β-Cys93) to form bioactive S-nitrosohemoglobin (SNO-Hb), and that efficient production of SNO-Hb requires selective processing of NO within the β-subunits. Bioactive SNO-Hb is localized primarily to the RBC membrane through interaction with Band 3, the transmembrane anion-exchanger 1 protein (AE1). Upon deoxygenation, transfer of the NO group from β-Cys93 of Hb to a cysteine thiol within AE1 serves the RBC vasodilator activity. In this way, O2 binding in Hb modulates the release of NO bioactivity. We further show that RBC NO bioactivity is inversely proportional to pO2 and impaired in disease. In an aortic ring bioassay sparged with variable concentrations of O2, addition of normal human RBCs elicited graded responses from relaxation at tissue pO2 (~3–7 mm Hg, hypoxic vasodilation), to loss of relaxation and progressively greater contractions at pO2’s of 10–63 mm Hg (hyperoxic vasoconstriction). Notably, RBC SNO-Hb levels and hypoxic vasodilation are impaired in several diseases characterized by vascular dysfunction. For example, in RBCs from patients with pulmonary arterial hypertension (PAH), we found decreased (13% of control) SNO-Hb content (assessed by photolysis-chemiluminescence) and impaired O2-dependent vasodilation (bioassay). RBCs from patients with other ischemic disorders have also been examined: RBCs demonstrate a pathogenesis-based impairment in their ability to mediate hypoxic vasodilation by NO. These results confirm the (patho)physiologic importance of RBC NO, and suggest that RBC dysfunction may contribute to impaired blood flow in diseases of the heart, lung and blood.


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