Vascular endothelial cells (ECs) are exposed to hemodynamic forces, which modulate EC functions and vascular biology/pathobiology in health and disease. The flow patterns and hemodynamic forces are not uniform in the vascular system. In straight parts of the arterial tree, blood flow is generally laminar and wall shear stress is high and directed; in branches and curvatures, blood flow is disturbed with nonuniform and irregular distribution of low wall shear stress. Sustained laminar flow with high shear stress upregulates expressions of EC genes and proteins that are protective against atherosclerosis, whereas disturbed flow with associated reciprocating, low shear stress generally upregulates the EC genes and proteins that promote atherogenesis. These findings have led to the concept that the disturbed flow pattern in branch points and curvatures causes the preferential localization of atherosclerotic lesions. Disturbed flow also results in postsurgical neointimal hyperplasia and contributes to pathophysiology of clinical conditions such as in-stent restenosis, vein bypass graft failure, and transplant vasculopathy, as well as aortic valve calcification. In the venous system, disturbed flow resulting from reflux, outflow obstruction, and/or stasis leads to venous inflammation and thrombosis, and hence the development of chronic venous diseases. Understanding of the effects of disturbed flow on ECs can provide mechanistic insights into the role of complex flow patterns in pathogenesis of vascular diseases and can help to elucidate the phenotypic and functional differences between quiescent (nonatherogenic/nonthrombogenic) and activated (atherogenic/thrombogenic) ECs. This review summarizes the current knowledge on the role of disturbed flow in EC physiology and pathophysiology, as well as its clinical implications. Such information can contribute to our understanding of the etiology of lesion development in vascular niches with disturbed flow and help to generate new approaches for therapeutic interventions.

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Effects of Disturbed Flow on Vascular Endothelium: Pathophysiological Basis and Clinical Perspectives

Cell isolation in designated regions or from heterogeneous samples is often required for many microfluidic cell-based assays. However, current techniques have either limited throughput or are incapable of viable off-chip collection. We present an innovative approach, allowing high-throughput and label-free cell isolation and enrichment from heterogeneous solution using cell size as a biomarker. The approach utilizes the irreversible migration of particles into microscale vortices, developed in parallel expansion-contraction trapping reservoirs, as the cell isolation mechanism. We empirically determined the critical particle∕cell diameter D(crt) and the operational flow rate above which trapping of cells∕particles in microvortices is initiated. Using this approach we successfully separated larger cancer cells spiked in blood from the smaller blood cells with processing rates as high as 7.5×10(6) cells∕s. Viable long-term culture was established using cells collected off-chip, suggesting that the proposed technique would be useful for clinical and research applications in which in vitro culture is often desired. The presented technology improves on current technology by enriching cells based on size without clogging mechanical filters, employing only a simple single-layered microfluidic device and processing cell solutions at the ml∕min scale.

http://www.rowland.harvard.edu/rjf/hur/Docs/Biomicrofluidics2011.pdf

High-throughput size-based rare cell enrichment using microscale vortices.

To elucidate the connection between blood flow and the localized genesis and development of atherosclerosis and thrombosis at the human carotid artery bifurcation, detailed studies of the flow patterns and distributions of fluid velocity and wall shear rate in this region were carried out using a transparent segment of the carotid artery, prepared from a human subject postmortem, and cinemicrographic techniques. It was found that a recirculation zone which consisted of a pair of complex spiral secondary flows, symmetrical about the common median plane of the bifurcation, was formed in the carotid sinus over wide ranges of inflow Reynolds numbers, Re0, and flow rate ratios, Q1/Q0 (internal/common). The formation and the size of the recirculation zone were largely dependent on Q1/Q0, as well as on Re0. The size of the recirculation zone increased from approximately 4 mm at Re0 = 300 to a maximum of approximately 9 mm at Re0 greater than 800. The results suggest that, under physiological conditions (Re0 approximately 600, Q1/Q0 approximately 0.7), a standing recirculation zone exists in the carotid sinus, thereby affecting local mass transfer and interactions of blood cells with the vessel wall, which may lead to the incidence of atherosclerosis and thrombosis in this region.

https://www.ahajournals.org/doi/pdf/10.1161/01.STR.15.1.50

Flow patterns in the human carotid artery bifurcation.

Adhesion of human platelets to collagen on the walls distal to a tubular expansion

An introduction to biofluid mechanics—basic models and applications

The behaviour of human and frog red cells, platelets and rigid spheres were studied in the annular vortex formed in steady or pulsatile flow at the sudden concentric expansion of a 151 $\mu$ m into 504 $\mu$ m diameter glass tube. During a single orbit the measured particle velocities and paths in steady flow were in good agreement with those calculated for the fluid, predicted by theory to circulate in closed orbits. Over longer periods, however, single blood cells and latex spheres $\mu$ m diameter migrated across the streamlines out of the vortex at a rate depending on the Reynolds number whereas spheres and aggregates of red cells > 30 $\mu$ m diameter remained in the vortex at all Reynolds numbers. Similar behaviour was noted in pulsatile flow when the vortex moved in phase with upstream fluid velocity and particles described spiral orbits of continually changing diameter. With red cell suspensions of 15-45% haematocrit in steady flow, migration of the corpuscles was also observed and resulted in the formation of a particle-free vortex. In pulsatile flow, cells were always present in the vortex, but their concentration which varied periodically was lower than that in the mainstream. The formation of aggregates of latex spheres and human platelets through collisions occurring in orbit, and their migration to the vortex centre was also observed.

H. L. Goldsmith

Papers

Flow behaviour of blood cells and rigid spheres in an annular vortex.