Biorheology最新文献

Background: Ultrastructural investigations of the endothelial glycocalyx reveal a layer adjacent to the cell surface with a structure consistent with the primary  ultrafilter of vascular walls. Theory predicts this layer can be no greater than 200-300 nm thick, a result  to be reconciled with observations that red cells and large macromolecules are excluded  from a region 1 micrometer or more from the cell membrane.

Objective: To determine whether this apparent inconsistency might be accounted for by a model of steady state water and protein transport through a glycocalyx bi-layer formed by a porous outer layer in series with a more selective inner layer.

Methods: Expressions for coupled water and albumin fluxes through the two layers were used to describe steady state ultra-filtration though the bi-layer model.

Results: Albumin accumulates at the interface between the porous layer and the selective inner layer. The osmotic pressure of accumulated albumin significantly modifies the observed permeability properties of the microvessel wall by an effective unstirred layer effect.

Conclusions: The model places significant constraints on the outer layer permeability properties . The only outer layer properties that are consistent with measured steady state filtration rates and models of red cell flux through microvessels are an albumin permeability coefficient and hydraulic conductivity more than an order of magnitude larger than the those of the inner layer.

Background: Atherosclerotic lesions develop preferentially at certain sites in the human arterial system, such as the inner wall of curved segments and the outer wall of bifurcations. Local wall shear stress (WSS) and concentration of low density lipoprotein (LDL) have been identified as two important factors contributing to these lesions.

Objective: To determine if a connection exists between arterial curvature and the formation of atherosclerosis.

Methods: A set of 3-D vessel models with different bend angles was constructed. By comparing blood flow, WSS, and LDL aggregation, the influence of bend curvature on atherosclerotic lesions was assessed.

Results: Upon increasing arterial bending, low WSS regions were formed at the outer wall of the junction between straight and curved segments, as well as the inner wall of curved segments. However, high LDL concentrations only appeared at the inner wall of the bend region. A connection between secondary flow and LDL concentration was observed; high LDL concentration regions had stronger secondary flow. Higher water infiltration velocity could enhance LDL aggregation, while blood non-Newtonian properties, by easing secondary flow, diminished its aggregation.

Conclusions: Under the same flow rate, a larger bend angle increased flow resistance, lowered WSS, and increased LDL surface concentrations, thus indicating an increased risk of atherosclerosis.

Background: The onset of many disease processes depends on the function of the endothelial cell (EC) glycocalyx (GCX) which acts as a flow-dependent barrier to cellular infiltration and molecular transport across the blood vessel wall.

Objective: This review aims to examine these processes with the potential end goal of implementing GCX repair to restore EC barrier function and slow the progression of disease.

Methods: Cell and mouse studies were employed to examine the state of EC GCX in healthy versus disruptive flow conditions. Correlations of observations of the GCX with a number of EC functions were sought with an emphasis on studies of trans-endothelial barrier integrity against vessel wall infiltration of cells and molecules from the circulation. To demonstrate the importance of GCX as a regulator of trans-endothelial infiltration, assays were performed using ECs with an intact GCX and compared to assays of ECs with an experimentally degraded GCX. Studies were also conducted of ECs in which a degraded GCX was repaired.

Results: In healthy flow conditions, the EC GCX was found to be thick and substantially covered the endothelial surface. GCX expression dropped significantly in complex flow conditions and coincided with a disease-like cellular and molecular accumulation in the endothelium or within the blood vessel wall. Therapeutic repair of the GCX abolished this accumulation.

Conclusions: Regenerating the degraded GCX reverses EC barrier dysfunction and may attenuate the progression of vascular disease.

Diabetic retinopathy is known as a microvascular complication of hyperglycemia, with a breakdown of the blood-retinal barrier, loss of pericytes, formation of microhemorrhages, early decreases in perfusion and areas of ischemia, with the latter speculated to induce the eventual proliferative, angiogenic phase of the disease. Our animal models of diabetic retinopathy demonstrate similar decreases in retinal blood flow as seen in the early stages of diabetes in humans. Our studies also show an alteration in the retinal distribution of red blood cells, with the deep capillary layer receiving a reduced fraction, and with flow being diverted more towards the superficial vascular layer. Normal red blood cell distribution is dependent on the presence of the endothelial surface layer, specifically the glycocalyx, which has been reported to be partially lost in the diabetic retina of both humans and animals. This review addresses these two phenomena in diabetes: altered perfusion patterns and loss of the glycocalyx, with a possible connection between the two.

Background: The endothelial glycocalyx plays a pivotal role in regulating blood flow, filtering blood components, sensing and transducing mechanical signals. These functions are intimately related to its dynamics at the molecular level.

Objective: The objective of this research is to establish the relationship between the functions of the endothelial glycocalyx and its dynamics at the molecular level.

Methods: To establish such a relationship, large-scale molecular dynamics simulations were undertaken to mimic the dynamics of the glycocalyx and its components in the presence of flow shear stresses.

Results: First, motions of the glycocalyx core protein and the pertinent subdomains were scrutinised. Three-directional movements of the glycocalyx core protein were observed, although the flow was imposed only in the x direction. Such an observation contributes to understanding the glycocalyx redistribution as reported in experiments. Unsynchronised motion of the core protein subdomains was also spotted, which provides an alternative explanation of macroscopic phenomena. Moreover, the dynamics, root-mean-square-deviations and conformational changes of the sugar chains were investigated. Based on the findings, an alternative force transmission pathway, the role of sugar chains, and potential influence on signalling transduction pathways were proposed and discussed.

Conclusions: This study relates the functions of the glycocalyx with its microscopic dynamics, which fills a knowledge gap about the links between different scales.

The endothelial glycocalyx (eGlx) constitutes the first barrier to protein in all blood vessels. This is particularly noteworthy in the renal glomerulus, an ultrafiltration barrier. Leakage of protein, such as albumin, across glomerular capillaries results in albumin in the urine (albuminuria). This is a hall mark of kidney disease and can reflect loss of blood vessel integrity in microvascular beds elsewhere. We discuss evidence demonstrating that targeted damage to the glomerular eGlx results in increased glomerular albumin permeability. EGlx is lost in diabetes and experimental models demonstrate loss from glomerular endothelial cells. Vascular endothelial growth factor (VEGF)A is upregulated in early diabetes, which is associated with albuminuria. Treatment with paracrine growth factors such as VEGFC, VEGF165b and angiopoietin-1 can modify VEGFA signalling, rescue albumin permeability and restore glomerular eGlx in models of diabetes. Manipulation of VEGF receptor 2 signalling, or a common eGlx biosynthesis pathway by these growth factors, may protect and restore the eGlx layer. This would help to direct future therapeutics in diabetic nephropathy.

Background: Mesenchymal stem cells (MSC) are used in therapy, often by injection into the blood.

Objective: We aimed to compare the adhesive and migratory properties of MSC from umbilical cords (UCMSC), bone marrow (BMMSC) or trabecular bone (TBMSC), which might influence delivery to injured tissue.

Methods: MSC were perfused through glass capillaries coated with matrix proteins, collagen or fibronectin, or albumin. Adherent cells were counted microscopically and their spreading analysed over time. MSC migration through 8 μm pore filters coated with the same proteins was analysed.

Results: The number of MSC adhering to collagen was greater than fibronectin, decreased as wall shear rate increased from 17 to 70 s-1, and was in the order UCMSC>BMMSC>TBMSC. Conversely, spreading was more effective on fibronectin and was in the order BMMSC>TBMSC≥UCMSC. Migration was promoted by coating the lower surface of filters with either matrix protein, with UCMSC migrating more efficiently than BMMSC.

Conclusions: MSC show origin-dependent variations in their efficiency of capture from flow and subsequent spreading or ability to migrate on matrix proteins. UCMSC showed most efficient capture from flow, which was followed by less spreading, but more rapid migration. These responses might be associated with more effective delivery from the circulation into damaged tissue.

Background: Previous studies on aneurysm modeling have focused on the blood rheology and vessel elasticity separately. The combined effects of blood shear thinning properties and wall elasticity need to be revealed.

Objective: To provide insights on how pulsatile hemodynamics vary with blood rheology and vessel elasticity for a developed abdominal aortic aneurysm (AAA).

Method: An Arbitrary Lagrangian-Eulerian fluid-solid interaction method is adopted with the Newtonian and the shear thinning Carreau constitutive models for the fluid with the linearly elastic and the hyperelastic Yeoh models for the vessel. Finite element based numerical solver is used to simulate the blood flow in the AAA.

Results: Newtonian model overestimates the velocity values compared to the Carreau model and the difference in the velocity field increases as the shear rate decreases at the instances of the cardiac cycle. The rigid walled simulations display higher deviations in the velocity and wall shear stress with the fluid rheology. The risk indicators show that Newtonian assumption combined with the linearly elastic model may overlook degeneration risk of arterial tissue.

Conclusions: Newtonian assumption for the blood as well as modelling the arterial wall as linearly elastic lead to significant differences in oscillatory hemodynamic properties with respect to the use of Carreau fluid together with hyperelastic vessel model, even in large vessel aneurysms.