Dataset Information

From Experiments to Simulation: Shear-Induced Responses of Red Blood Cells to Different Oxygen Saturation Levels.

ABSTRACT: Red blood cells (RBC) carry and deliver oxygen (O2) to peripheral tissues through different microcirculatory regions where they are exposed to various levels of shear stress (SS). O2 affinity of hemoglobin (Hb) decreases as the blood enters the microcirculation. This phenomenon determines Hb interactions with RBC membrane proteins that can further regulate the structure of cytoskeleton and affect the mechanical properties of cells. The goal of this study is to evaluate shear-induced RBC deformability and simulate RBC dynamics in blood flow under oxygenated and deoxygenated conditions. Venous blood samples from healthy donors were oxygenated with ambient air or deoxygenated with 100% nitrogen gas for 10 min and immediately applied into an ektacytometer (LORRCA). RBC deformability was measured before and after the application of continuous 5 Pa SS for 300 s by LORRCA and recorded as elongation index (EI) values. A computational model was generated for the simulation of blood flow in a real carotid artery section. EI distribution throughout the artery and its relationships with velocity, pressure, wall SS and viscosity were determined by computational tools. RBC deformability significantly increased in deoxygenation compared to oxygenated state both before and after 5 Pa SS implementation (p < 0.0001). However, EI values after continuous SS were not significant at higher SS levels (>5.15 Pa) in deoxygenated condition. Simulation results revealed that the velocity gradient dominates the generation of SS and the shear thinning effect of blood has a minor effect on it. Distribution of EI was calculated during oxygenation/deoxygenation which is 5-10 times higher around the vessel wall compared to the center of the lumen for sections of the pulsatile flow profile. The extent of RBC deformability increases as RBCs approach to the vessel wall in a real 3D artery model and this increment is higher for deoxygenated condition compared to the oxygenated state. Hypoxia significantly increases shear-induced RBC deformability. RBCs could regulate their own mechanical properties in blood flow by increasing their deformability in hypoxic conditions. Computational tools can be applied for defining hypoxia-mediated RBC deformability changes to monitor blood flow in hypoxic tissues.

SUBMITTER: Ugurel E

PROVIDER: S-EPMC6987081 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

From Experiments to Simulation: Shear-Induced Responses of Red Blood Cells to Different Oxygen Saturation Levels.

Ugurel Elif E Piskin Senol S Aksu Ali Cenk AC Eser Aysenur A Yalcin Ozlem O

Frontiers in physiology 20200122

Red blood cells (RBC) carry and deliver oxygen (O<sub>2</sub>) to peripheral tissues through different microcirculatory regions where they are exposed to various levels of shear stress (SS). O<sub>2</sub> affinity of hemoglobin (Hb) decreases as the blood enters the microcirculation. This phenomenon determines Hb interactions with RBC membrane proteins that can further regulate the structure of cytoskeleton and affect the mechanical properties of cells. The goal of this study is to evaluate shea ...[more]

PMID: 32038272

Similar Datasets

Project description:High-altitude (HA, 2500 m) hypoxic exposure evokes a multitude of physiological processes. The hypoxia-sensing genes though influence transcriptional output in disease susceptibility; the exact regulatory mechanisms remain undetermined in high-altitude pulmonary edema (HAPE). Here, we investigated the differential DNA methylation distribution in the two genes encoding the oxygen-sensing HIF-prolyl hydroxylases, prolyl hydroxylase domain protein 2 (PHD2) and factor inhibiting HIF-1α and the consequent contributions to the HAPE pathophysiology. Deep sequencing of the sodium bisulfite converted DNA segments of the two genes, Egl nine homolog 1 (EGLN1) and Hypoxia Inducible Factor 1 Subunit Alpha Inhibitor (HIF1AN), was conducted to analyze the differential methylation distribution in three study groups, namely HAPE-patients (HAPE-p), HAPE-free sojourners (HAPE-f) and healthy HA natives (HLs). HAPE-p and HAPE-f were permanent residents of low altitude (< 200 m) of North India who traveled to Leh (3500 m), India, and were recruited through Sonam Norboo Memorial (SNM) hospital, Leh. HLs were permanent residents of altitudes at and above 3500 m. In addition to the high resolution, bisulfite converted DNA sequencing, gene expression of EGLN1 and HIF1AN and their plasma protein levels were estimated. A significantly lower methylation distribution of CpG sites was observed in EGLN1 and higher in HIF1AN (P < 0.01) in HAPE-p compared to the two control groups, HAPE-f and HLs. Of note, differential methylation distribution of a few CpG sites, 231,556,748, 231,556,804, 231,556,881, 231,557,317 and 231,557,329, in EGLN1 were significantly associated with the risk of HAPE (OR = 4.79-10.29; P = 0.048-004). Overall, the methylation percentage in EGLN1 correlated with upregulated plasma PHD2 levels (R = - 0.36, P = 0.002) and decreased peripheral blood oxygen saturation (SpO2) levels (R = 0.34, P = 0.004). We also identified a few regulatory SNPs in the DNA methylation region of EGLN1 covering chr1:231,556,683-231,558,443 suggestive of the functional role of differential methylation distribution of these CpG sites in the regulation of the genes and consequently in the HIF-1α signaling. Significantly lower methylation distribution in EGLN1 and the consequent physiological influences annotated its functional epigenetic relevance in the HAPE pathophysiology.

Dataset Information

From Experiments to Simulation: Shear-Induced Responses of Red Blood Cells to Different Oxygen Saturation Levels.

Publications

From Experiments to Simulation: Shear-Induced Responses of Red Blood Cells to Different Oxygen Saturation Levels.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets