Modeling of biomechanics and biorheology of red blood cells in type-2 diabetes mellitus

Chang, Hung-Yu; Li, Xuejin; Karniadakis, George Em

doi:10.1101/132134

Cited by 3 publications

(3 citation statements)

References 83 publications

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“…For example, retinal vascular endothelial cells may have impaired ability to liberate endothelial nitric oxide synthase, thus affecting retinal vascular autoregulation. In addition, enhanced plasma viscosity, increased platelet aggregation, and decreased red blood cell deformability also lead to retinal and ONH perfusion problems . Fundamental structural alterations of capillaries in diabetes including endothelium dysfunction, vascular basement membrane thickening, pericyte apoptosis and capillary occlusion also involve small blood vessels in the ONH …”

Section: Discussionmentioning

confidence: 99%

Optic nerve head perfusion changes preceding peripapillary retinal nerve fibre layer thinning in preclinical diabetic retinopathy

Cao

Yang

et al. 2018

Clinical Exper Ophthalmology

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Section: Discussionmentioning

confidence: 99%

Optic nerve head perfusion changes preceding peripapillary retinal nerve fibre layer thinning in preclinical diabetic retinopathy

Cao

Yang

et al. 2018

Clinical Exper Ophthalmology

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“…We found that, in agreement with the experiments, margination of micro-beads increases with size and shear rate. We have introduced and validated a T2DM RBC model in our previous work (47). Here, we adopted the same red cell model for modeling the diabetic blood, whereas a T2DM platelet model is built based on the parameters informed by the clinical blood analysis of 64 diabetic patients.…”

Section: Resultsmentioning

confidence: 99%

“…Although the alteration in the size and shape of diabetic RBCs is still debatable and probably dependent on glycemic control of the study subjects, we considered extreme values for S/V that reported by Jin et al (56). We have recently proposed a T2DM RBC model (47), which has been validated with available experimental data. Following our previous study, here, we extend our T2DM RBC model (DRBC) to a suspension with cell properties similar to those of a NRBC except for a shear modulus, µ s = 2µ 0 (µ 0 is the shear modulus of healthy subjects), and a reduced S/V ratio, S/V = 1.04.…”

Section: Parameter Estimation Rbc Modelsmentioning

confidence: 97%

Quantifying Platelet Margination in Diabetic Blood Flow

Chang

Yazdani

et al. 2018

Preprint

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Patients with type 2 diabetes mellitus (T2DM) develop thrombotic abnormalities strongly associated with cardiovascular diseases. In addition to the changes of numerous coagulation factors such as elevated levels of thrombin and fibrinogen, the abnormal rheological effects of red blood cells (RBCs) and platelets flowing in blood are crucial in platelet adhesion and thrombus formation in T2DM. An important process contributing to the latter is the platelet margination. We employ the dissipative particle dynamics method to seamlessly model cells, plasma, and vessel walls. We perform a systematic study on the RBC and platelet transport in cylindrical vessels by considering different cell shapes, sizes and RBC deformabilities in healthy and T2DM blood, as well as variable flowrates and hematocrit. In particular, we use cellular-level RBC and platelet models with parameters derived from patient-specific data and present a sensitivity study. We find T2DM RBCs, which are less deformable compared to normal RBCs, lower the transport of platelets toward the vessel walls whereas platelets with higher mean volume (often observed in T2DM) lead to enhanced margination. Furthermore, increasing the flowrate or hematocrit enhances platelet margination. We also investigated the effect of platelet shape and observed a non-monotonic variation with the highest near-wall concentration corresponding to platelets with moderate aspect ratio of 0.38. We examine the role of white blood cells (WBCs), whose count is increased notably in T2DM patients. We find that WBC rolling or WBC adhesion tend to decrease platelet margination due to hydrodynamic effects. To the best of our knowledge, such simulations of blood including all blood cells have not been performed before, and our quantitative findings can help separate the effects of hydrodynamic interactions from adhesive interactions, and potentially shed light on the associated pathological processes in T2DM such as increased inflammatory response, platelet activation and adhesion, and ultimately thrombus formation. METHODSWe employ dissipative particle dynamics (DPD) to model whole blood flow, i.e. plasma, RBCs, platelets and WBCs, in 40-micron diameter vessels. DPD is a coarse-grained analog of molecular dynamics, where each particle represents a lump of molecules that interacts with other particles through soft pairwise forces. In addition to blood plasma modeled by collections of free DPD particles, the membrane of suspending cells including RBCs, platelets, and WBCs is constructed by a 2D triangulated network with N v vertices (DPD particles).These vertices are connected by N s elastic bonds to impose proper membrane mechanics. More details of hydrodynamic interactions between DPD particles, and models for blood cells are presented in Appendix A. We also validated systematically the DPD model by simulating the margination of spherical particles of different sizes in blood flow and compared against recent experimental measurements (52). The validation results are given in Appendix B.

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Enhanced three-dimensional particle detection in microcirculation experiments with defocus particle tracking and ghost red blood cells

Coutinho,

Warlitz,

Silva-Santos

et al. 2024

Exp Fluids

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Experimental investigations on the motion of rigid particles in microcirculation environments are still scarce owing to the three-dimensional (3D) motion of the particles and to the particle image masking due to the presence of the red blood cells (RBCs). Despite the recent progress on the 3D tracking of rigid particles in RBC flows with defocus particle tracking (DPT) methods, the problem of particle image masking remains to be solved. Here, we propose, test, and evaluate the use hemoglobin-free RBCs, also known as ghost RBCs, as a replacement for normal RBCs in experiments with rigid particles in microcirculation environments. We performed DPT measurements of a pressure-driven flow of normal and ghost RBC suspensions seeded with rigid particles at three different flow rates. We show that the quasi-transparent appearance of ghost RBCs, as a result of the lack of hemoglobin, eliminates the RBC-induced masking of the defocused particle images and allows to achieve the particle matching standards found in cell-free experiments. In fact, ghost RBC suspensions enable the tracking of the rigid particles across the entire height of the microchannel, which was not possible in normal RBC flows. On a fluid dynamic level, we show that ghost RBC suspensions provide similar conditions to normal RBCs in terms of the velocity of the rigid particles and the rigid particles exhibit similar lateral dynamics in both types of cell suspensions. In essence, the findings from this work demonstrate that ghost RBCs are a well-suited replacement for normal RBCs in experiments aiming at deciphering the motion of rigid particles in microcirculation environments. Graphical abstract

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Modeling of biomechanics and biorheology of red blood cells in type-2 diabetes mellitus

Cited by 3 publications

References 83 publications

Optic nerve head perfusion changes preceding peripapillary retinal nerve fibre layer thinning in preclinical diabetic retinopathy

Optic nerve head perfusion changes preceding peripapillary retinal nerve fibre layer thinning in preclinical diabetic retinopathy

Quantifying Platelet Margination in Diabetic Blood Flow

Enhanced three-dimensional particle detection in microcirculation experiments with defocus particle tracking and ghost red blood cells

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