Quantification of wall shear stress in large blood vessels using Lagrangian interpolation functions with cine phase-contrast magnetic resonance imaging

Arterial wall shear stress is hypothesized to be an important factor in the localization of atherosclerosis. Current methods to compute wall shear stress from magnetic resonance imaging (MRI) data do not account for flow profiles characteristic of pulsatile flow in noncircular vessel lumens. We describe a method to quantify wall shear stress in large blood vessels by differentiating velocity interpolation functions defined using cine phase-contrast MRI data on a band of elements in the neighborhood of the vessel wall. Validation was performed with software phantoms and an in vitro flow phantom. At an image resolution corresponding to in vivo imaging data of the human abdominal aorta, time-averaged, spatially averaged wall shear stress for steady and pulsatile flow were determined to be within 16% and 23% of the analytic solution, respectively. These errors were reduced to 5% and 8% with doubling in image resolution. For the pulsatile software phantom, the oscillation in shear stress was predicted to within 5%. The mean absolute error of circumferentially resolved shear stress for the nonaxisymmetric phantom decreased from 28% to 15% with a doubling in image resolution. The irregularly shaped phantom and in vitro investigation demonstrated convergence of the calculated values with increased image resolution. We quantified the shear stress at the supraceliac and infrarenal regions of a human abdominal aorta to be 3.4 and 2.3 dyn/cm², respectively. © 2002 Biomedical Engineering Society. PAC2002: 8761-c, 8719Uv     

Theoretical prediction of low-density lipoproteins concentration at the luminal surface of an artery with a multiple bend

To elucidate the mechanisms of localization of atherosclerotic lesions in man, the effects of various physical and hemodynamic factors on transport of atherogenic low-density lipoproteins (LDL) from flowing blood to the wall of an artery with a multiple bend were studied theoretically by means of a computer simulation under the conditions of a steady flow. It was found that due to a semipermeable nature of an arterial wall to plasma, flow-dependent concentration polarization of LDL occurred at the luminal surface of the vessel, creating a region of high LDL concentration distal to the apex of the inner wall of each bend where the flow was locally disturbed by the formation of secondary and recirculation flows and where wall shear stresses were low. The highest surface concentration of LDL occurred distal to the acute second bend where atherosclerotic intimal thickening developed. At a Re₀=500, the values calculated using estimated diffusivities of LDL in whole blood and plasma were respectively 35.1% and 15.6% higher than that in the bulk flow. The results are consistent with our hypothesis that the localization of atherosclerotic lesions results from the flow-dependent concentration polarization of LDL which creates locally a hypercholesterolemic environment even in normocholesterolemic subjects, thus augmenting the uptake of LDL by vascular endothelial cells existing at such sites. © 2002 Biomedical Engineering Society. PAC2002: 8719Uv, 8719Xx, 8714Ee, 8716Uv     

Lipid Deposition in Rat Aortas with Intraluminal Hemispherical Plug Stenosis : A Morphological and Biophysical Study

A new method was devised to create a stenosis in the rat abdominal aorta. To restrict blood flow, a hemispherical plug was inserted into the aorta through a renal artery. This type of intrinsic (intraluminal) stenosis minimizes possible intramural effects associated with external compression or ligation which severely deform the arterial wall. In the aorta of hypercholesterolemic rats, lipid deposits were distributed in crescent-shaped patches proximal and distal to the plug, whereas lipid deposition in the opposite aortic wall was inhibited. Based on enlarged physical scale models used to study the flow field, the regions of lipid deposition were found to coincide with regions of low shear stress, stagnation, and recirculation. Shear stress was elevated at the wall opposite the plug. These results show that when confounding mural effects are minimized, lipid deposition is promoted in regions of low shear stress with recirculation and inhibited in regions of elevated shear stress.     

Correlation between local hemodynamics and lesion distribution in a novel aortic regurgitation murine model of atherosclerosis

Following surgical induction of aortic valve regurgitation (AR), extensive atherosclerotic plaque development along the descending thoracic and abdominal aorta of Ldlr ^−/− mice has been reported, with distinct spatial distributions suggestive of a strong local hemodynamic influence. The objective of this study was to test, using image-based computational fluid dynamics (CFD), whether this is indeed the case. The lumen geometry was reconstructed from micro-CT scanning of a control Ldlr ^−/− mouse, and CFD simulations were carried out for both AR and control flow conditions derived from Doppler ultrasound measurements and literature data. Maps of time-averaged wall shear stress magnitude (TAWSS), oscillatory shear index (OSI) and relative residence time (RRT) were compared against the spatial distributions of plaque stained with oil red O, previously acquired in a group of AR and control mice. Maps of OSI and RRT were found to be consistent with plaque distributions in the AR mice and the absence of plaque in the control mice. TAWSS was uniformly lower under control vs. AR flow conditions, suggesting that levels (>100 dyn/cm²) exceeded those required to alone induce a pro-atherogenic response. Simulations of a straightened CFD model confirmed the importance of anatomical curvature for explaining the spatial distribution of lesions in the AR mice. In summary, oscillatory and retrograde flow induced in the AR mice, without concomitant low shear, may exacerbate or accelerate lesion formation, but the distinct anatomical curvature of the mouse aorta is responsible for the spatial distribution of lesions.     

Quantification of particle residence time in abdominal aortic aneurysms using magnetic resonance imaging and computational fluid dynamics

Hemodynamic conditions are hypothesized to affect the initiation, growth, and rupture of abdominal aortic aneurysms (AAAs), a vascular disease characterized by progressive wall degradation and enlargement of the abdominal aorta. This study aims to use magnetic resonance imaging (MRI) and computational fluid dynamics (CFD) to quantify flow stagnation and recirculation in eight AAAs by computing particle residence time (PRT). Specifically, we used gadolinium-enhanced MR angiography to obtain images of the vessel lumens, which were used to generate subject-specific models. We also used phase-contrast MRI to measure blood flow at supraceliac and infrarenal locations to prescribe physiologic boundary conditions. CFD was used to simulate pulsatile flow, and PRT, particle residence index, and particle half-life of PRT in the aneurysms were computed. We observed significant regional differences of PRT in the aneurysms with localized patterns that differed depending on aneurysm geometry and infrarenal flow. A bulbous aneurysm with the lowest mean infrarenal flow demonstrated the slowest particle clearance. In addition, improvements in particle clearance were observed with increase of mean infrarenal flow. We postulate that augmentation of mean infrarenal flow during exercise may reduce chronic flow stasis that may influence mural thrombus burden, degradation of the vessel wall, and aneurysm growth.     

腹主动脉叉血流动力学边界元分析

本文利用边界元方法计算了腹主动脉叉。在动脉粥样硬化前后的血液流场、血管壁切应力等血液流体动力学特性,通过对动脉粥样硬化产生前后,左、右髂总动脉壁切应力的计算结果分析,对粥样斑块病变产生和发展的血液流体动力学原因做出了判断。结果显示:腹主动脉叉几何形状的不对称性导致分叉处血液流速、血管壁切应力分布的不对称,内侧壁切应力大于外侧壁,右髂总动脉内侧壁切应力大于左髂总动脉。动脉粥样硬化处由于血管腔变窄血液流速明显变大、切应力变大,容易使斑块表面撕裂出现组织增生,粥样斑块下游处血流速度、切应力减小,形成血液分离区,使血细胞聚集,造成动脉粥样硬化发展、加剧。     

In vivo quantification of blood flow and wall shear stress in the human abdominal aorta during lower limb exercise

Magnetic resonance (MR) imaging techniques and a custom MR-compatible exercise bicycle were used to measure, in vivo, the effects of exercise on hemodynamic conditions in the abdominal aorta of eleven young, healthy subjects. Heart rate increased from 73±6.2 beats/min at rest to 110±8.8 beats/min during exercise (p < 0.0001). The total blood flow through the abdominal aorta increased from 2.9±0.6 L/min at rest to 7.2±1.4 L/min during exercise (p < 0.0005) while blood flow to the digestive and renal circulations decreased from 2.1±0.5 L/min at rest to 1.6±0.7 L/min during exercise (p < 0.01). Infrarenal blood flow increased from 0.9±0.4 L/min at rest to 5.6±1.1 L/min during exercise (p < 0.0005). Wall shear stress increased in the supraceliac aorta from 3.5±0.8 dyn/cm² at rest to 6.2±0.5 dyn/cm² during exercise (p < 0.0005) and increased in the infrarenal aorta from 1.3±0.8 dyn/cm² at rest to 5.2±1.3 dyn/cm² during exercise (p < 0.0005). © 2002 Biomedical Engineering Society. PAC2002: 8719Uv, 8761-c     

Influence of Vasoactive Drugs on Wall Shear Stress Distribution in the Abdominal Aortic Bifurcation: An In Vitro Study

The present study compares the wall shear stress (rate) distribution in a compliant aortic bifurcation model under three different hemodynamic states: normal state, angiotensin II infusion state (vasoconstrictor), and isoproterenol infusion state (vasodilator). Using a Newtonian blood analog fluid, flow wave forms corresponding to each flow state were generated in an in vitro flow loop and a photographic flow visualization technique was employed to measure wall shear rate. The results indicate a zone of low mean wall shear stress and highly oscillatory shear stress on the outer (lateral) wall of the bifurcation. In this zone, the mean wall shear stress became negative for all three hemodynamic states indicating flow separation. However, the spatial extent of the flow separation zone was not affected significantly by the flow state. The study also revealed a large spatial variation of the phase angle between the hoop strain (circumferential strain due to radial artery expansion) and the wall shear stress, the two main mechanical stimuli acting on endothelial cells which affect their biology. In the zone of low mean wall shear stress on the outer wall, the two stimuli were more out of phase relative to the mother branch, whereas they were less out of phase (by about 50°) on the inner wall (flow divider side). This phase angle was affected significantly by the flow state. For angiotensin II, the phase angle reached a maximum of 125° in the low mean shear zone while the maximum was 94° and 66° for the normal and isoproterenol states, respectively. Our observation that large phase angles between the hoop strain and wall shear stress wave forms are localized in the low shear stress region where atherosclerotic disease occurs suggests the possible physiological relevance of this phase angle to the development of atherosclerosis. © 1998 Biomedical Engineering Society. PAC98: 8745Hw     

The Flow Field along the Entire Length of Mouse Aorta and Primary Branches

There is a spatial disposition to atherosclerosis along the aorta corresponding to regions of flow disturbances. The objective of the present study is to investigate the detailed distribution of hemodynamic parameters (wall shear stress (WSS), spatial gradient of wall shear stress (WSSG), and oscillatory shear index (OSI)) in the entire length of C57BL/6 mouse aorta with all primary branches (from ascending aorta to common iliac bifurcation). The detailed geometrical parameters (e.g., diameter and length of the vessels) were obtained from casts of entire aorta and primary branches of mice. The flow velocity was measured at the inlet of ascending aorta using Doppler flowprobe in mice. The outlet pressure boundary condition was estimated based on scaling law. The continuity and Navier–Stokes equations were solved using three-dimensional finite element method (FEM). The model prediction was tested by comparing the computed flow rate with the flow rate measured just before the common iliac bifurcation, and good agreement was found. It was also found that complex flow patterns occur at bifurcations between main trunk and branches. The major branches of terminal aorta, with the highest proportion of atherosclerosis, have the lowest WSS, and the relatively atherosclerotic-prone aortic arch has much more complex WSS distribution and higher OSI value than other sites. The low WSS coincides with the high OSI, which approximately obeys a power law relationship. Furthermore, the scaling law between flow and diameter holds in the entire aorta and primary branches of mice under pulsatile blood flow conditions. This model will eventually serve to elucidate the causal relation between hemodynamic patterns and atherogenesis in KO mice.     

Neutrophil Adhesion on Endothelial Cells in a Novel Asymmetric Stenosis Model: Effect of Wall Shear Stress Gradients

Leukocytes play a pivotal role in the progression of atherosclerosis. A novel three-dimensional in vitro asymmetric stenosis model was used to better investigate the role of local hemodynamics in the adhesion of leukocytes to an established plaque. The adhesion of a human promyelocytic cell line (NB4) on a human abdominal aortic endothelial cell (EC) monolayer was quantified. NB4 cells were circulated over TNF-α stimulated and nonstimulated ECs for 1 or 6 h at 1.25 or 6.25 dynes/cm² and compared to static conditions. Cytokine stimulation increased significantly EC expression of intercellular adhesion molecule and vascular cell adhesion molecule. Under static conditions, neutrophils adhered overall more than under flow, with decreased adhesion with increasing shear. Adhesion was significantly higher in the recirculation region distal to the stenosis than in the inlet. Preshearing the ECs decreased the expression of cell adhesion molecules in inflamed endothelium and significantly decreased adhesion. However, the ratio of adhesion between the recirculation zone and the inlet increased, hence exhibiting an increased regional difference. This work suggests an important role for neutrophil–EC interactions in the atherosclerotic process, especially in wall shear stress gradient regions. This is important clinically, potentially helping to explain plaque stability.     

腹主动脉瘤的数值计算模型比较研究

目的分别采用纯流体模型和流固耦合模型来计算腹主动脉瘤的血流动力学特征,比较两种数值模型的不同,并讨论在研究腹主动脉瘤中的应用。方法使用Gambit 2.2.30和COMSOL Multiphysics 4.2建立腹主动脉瘤的理想模型,分别基于有限体的方法分析纯流体模型,基于任意拉格朗日-欧拉算法(Arbitrary Lagrangian-Eulerian)计算流固耦合模型。结果同样的入口速度下,纯流体模型出现4个涡流和6个局部压力集中;流固耦合模型只有2个涡流和局部压力集中,且涡流中心更接近腹主动脉瘤的远端。在边界层分离点、血流回帖位置以及腹主动脉瘤的近端和远端,两种模型均出现壁剪切力极值。血管壁的最大形变和最大壁应力出现在腹主动脉瘤的近端和远端。结论两种模型的涡流个数和涡流中心的位置均不一样,与瘤体的生长有着密切的关联;流固耦合模型中的最大壁剪切力比纯流体模型要小36%;最大壁应力和最大血管壁的形变量与出口血压呈正相关。在研究血管瘤生长与血流动力学的关系时需要考虑使用流固耦合模型。     

Hemodynamics of the Normal Aorta Compared to Fusiform and Saccular Abdominal Aortic Aneurysms with Emphasis on a Potential Thrombus Formation Mechanism

Abdominal Aortic Aneurysms (AAAs), i.e., focal enlargements of the aorta in the abdomen are frequently observed in the elderly population and their rupture is highly mortal. An intra-luminal thrombus is found in nearly all aneurysms of clinically relevant size and multiply affects the underlying wall. However, from a biomechanical perspective thrombus development and its relation to aneurysm rupture is still not clearly understood. In order to explore the impact of blood flow on thrombus development, normal aortas (n = 4), fusiform AAAs (n = 3), and saccular AAAs (n = 2) were compared on the basis of unsteady Computational Fluid Dynamics simulations. To this end patient-specific luminal geometries were segmented from Computerized Tomography Angiography data and five full heart cycles using physiologically realistic boundary conditions were analyzed. Simulations were carried out with computational grids of about half a million finite volume elements and the Carreau–Yasuda model captured the non-Newtonian behavior of blood. In contrast to the normal aorta the flow in aneurysm was highly disturbed and, particularly right after the neck, flow separation involving regions of high streaming velocities and high shear stresses were observed. Naturally, at the expanded sites of the aneurysm average flow velocity and wall shear stress were much lower compared to normal aortas. These findings suggest platelets activation right after the neck, i.e., within zones of pronounced recirculation, and platelet adhesion, i.e., thrombus formation, downstream. This mechanism is supported by recirculation zones promoting the advection of activated platelets to the wall.     

Factors Influencing Blood Flow Patterns in the Human Right Coronary Artery

Evidence suggests that atherogenesis is linked to local hemodynamic factors such as wall shear stress. We investigated the velocity and wall shear stress patterns within a human right coronary artery (RCA), an important site of atherosclerotic lesion development. Emphasis was placed on evaluating the effect of flow waveform and inlet flow velocity profile on the hemodynamics in the proximal, medial, and distal arterial regions. Using the finite-element method, velocity and wall shear stress patterns in a rigid, anatomically realistic model of a human RCA were computed. Steady flow simulations (Re_D=500) were performed with three different inlet velocity profiles; pulsatile flow simulations utilized two different flow waveforms (both with Womersley parameter=1.82, mean Re_D=233),1 as well as two of the three inlet profiles. Velocity profiles showed Dean-like secondary flow features that were remarkably sensitive to the local curvature of the RCA model. Particularly noteworthy was the rotation of these Dean-like profiles, which produced large local variations in wall shear stress along the sidewalls of the RCA model. Changes in the inlet velocity profiles did not produce significant changes in the arterial velocity and wall shear stress patterns. Pulsatile flow simulations exhibited remarkably similar cycle-average wall shear stress distributions regardless of waveform and inlet velocity profile. The oscillatory shear index was very small and was attributed to flow reversal in the waveform, rather than separation. Cumulatively, these results illustrate that geometric effects (particularly local three-dimensional curvature) dominate RCA hemodynamics, implying that studies attempting to link hemodynamics with atherogenesis should replicate the patient-specific RCA geometry. © 2001 Biomedical Engineering Society. PAC01: 8719Uv, 0270Dh, 8719Xx, 8710+e     

Effect of LVAD outflow conduit insertion angle on flow through the native aorta

Background and aim: The goal of this study was to evaluate the effect of surgical anastomosis configuration of the aortic outflow conduit (AOC) from a continuous flow left ventricular assist device (LVAD) on the flow fields in the aorta using CFD simulations. The geometry of the surgical integration of the LVAD is an important factor in the flow pattern that develops both in series (aortic valve closed, all flow through LVAD) and in parallel (heart pumping in addition to LVAD).

Methods: CFD models of the AOC junctions simulate geometry as cylindrical tubes that intersect at angles ranging from 30° to 90°. Velocity fields are computed over a range of cardiac output for both series and parallel flow.

Results: Our results demonstrate that the flow patterns are significantly affected by the angle of insertion of the AOC into the native aorta, both during series and parallel flow conditions. Zones of flow recirculation and high shear stress on the aortic wall can be observed at the highest angle, gradually decreasing in size until disappearing at the lowest angle of 30°. The highest velocity and shear stress values were associated with series flow.

Conclusions: The results suggest that connecting the LVAD outflow conduit to the proximal aorta at a shallower angle produces fewer secondary flow patterns in the native cardiovascular system.     

Hemodynamics analyses of arterial expansions with implications to thrombosis and restenosis

It is assumed that critical hemodynamic factors play an important role in the onset, localization and degree of post-operative complications, for example, thrombosis and restenosis. Of special interest are sudden expansion flows, which may occur in straight artery segments such as the common carotid after endarterectomy or end-to-end anastomoses. Sudden expansion geometries are possible origins of early post-operative emboli and significant myointimal hyperplasia resulting in early or late complications. Transient laminar axisymmetric and fully three-dimensional blood flows were simulated employing a validated finite volume code in conjunction with a Runge-Kutta particle tracking technique. Disturbed flow indicators, which may predict the onset of thrombosis and/or restenosis, were identified and employed to evaluate 90 degrees -step and smooth expansion geometries.Smooth expansion geometries have weaker disturbed flow features than step expansion geometries. Specifically, the regions near the expansion wall and the reattachment point are susceptible to both atherosclerotic lesion and thrombi formations as indicated by non-uniform hemodynamic indicators such as near-zero wall shear stress and elevated wall shear stress gradients as well as blood particle accumulation and deposition. A new parameter, the wall shear stress angle deviation (WSSAD) has been introduced, which indicates areas of abnormal endothelial cell morphology and particle wall deposition. In turn, regions of low wall shear stress and high wall shear stress gradients are recognized as susceptible sites for arterial diseases. Thus, it is interesting to note that high WSSAD surface areas cover low wall shear stress, high wall shear stress gradient locations as well as high wall particle deposition.A gradual change in step expansion geometry provides better results in terms of WSSAD values and hence potentially reducing atherosclerosis as well as thrombi formation.     

雌激素对血流动力学及多发性大动脉炎血管重构的影响

以多发性大动脉炎模型做试验,观察大动脉空间几何形态重构。测定血浆雌激素、孕激素和一氧化氮产物（NO     

Hemodynamic Changes Quantified in Abdominal Aortic Aneurysms with Increasing Exercise Intensity Using MR Exercise Imaging and Image-Based Computational Fluid Dynamics

Abdominal aortic aneurysm (AAA) is a vascular disease resulting in a permanent, localized enlargement of the abdominal aorta. We previously hypothesized that the progression of AAA may be slowed by altering the hemodynamics in the abdominal aorta through exercise [Dalman, R. L., M. M. Tedesco, J. Myers, and C. A. Taylor. Ann. N.Y. Acad. Sci. 1085:92–109, 2006]. To quantify the effect of exercise intensity on hemodynamic conditions in 10 AAA subjects at rest and during mild and moderate intensities of lower-limb exercise (defined as 33 ± 10% and 63 ± 18% increase above resting heart rate, respectively), we used magnetic resonance imaging and computational fluid dynamics techniques. Subject-specific models were constructed from magnetic resonance angiography data and physiologic boundary conditions were derived from measurements made during dynamic exercise. We measured the abdominal aortic blood flow at rest and during exercise, and quantified mean wall shear stress (MWSS), oscillatory shear index (OSI), and particle residence time (PRT). We observed that an increase in the level of activity correlated with an increase of MWSS and a decrease of OSI at three locations in the abdominal aorta, and these changes were most significant below the renal arteries. As the level of activity increased, PRT in the aneurysm was significantly decreased: 50% of particles were cleared out of AAAs within 1.36 ± 0.43, 0.34 ± 0.10, and 0.22 ± 0.06 s at rest, mild exercise, and moderate exercise levels, respectively. Most of the reduction of PRT occurred from rest to the mild exercise level, suggesting that mild exercise may be sufficient to reduce flow stasis in AAAs.     

Hemodynamic effects on atherosclerosis-prone coronary artery: wall shear stress/rate distribution and impedance phase angle in coronary and aortic circulation

The objective of the present study was to evaluate the hemodynamic characteristics of an atherosclerosis-prone coronary artery compared to the aorta. We describe three- dimensional spatial patterns of wall shear stress (WSS) according to the impedance phase angle in pulsatile coronary and aorta models using in vivo hemodynamic parameters and computed numerical simulations both qualitatively and quantitatively. Angiography of coronary arteries and aortas were done to obtain a standard model of vascular geometry. Simultaneously to the physiologic studies, flow-velocity and pressure profiles from in vivo data of the intravascular Doppler and pressure wire studies allowed us to include in vitro numerical simulations. Hemodynamic variables, such as flow-velocity, pressure and WSS in the coronary and aorta models were calculated taking into account the effects of vessel compliance and phase angle between pressure and flow waveforms. We found that there were spatial fluctuations of WSS and in the recirculation areas at the curved outer wall surface of the coronary artery. The mean WSS of the calculated negative phase angle increased in the coronary artery model over that in the aorta model and the phase angle effect was most prominent on the calculated amplitude of WSS of the coronary artery. This study suggests that the rheologic property of coronary circulation, such as the fluctuation of WSS/WSR induces several hemodynamic characteristics. A separation of flow-velocity, a difference in phase between pressure conductance and blood flow and prominent temporal and/or spatial oscillatory fluctuations of the shear forces as a function of pulsatile flow might be important factors in atherogenesis and progression of atherosclerosis.     

Fluid mechanics of arterial stenosis: Relationship to the development of mural thrombus

In this study, we analyzed blood flow through a model stenosis with Reynolds numbers ranging from 300 to 3,600 using both experimental and numerical methods. The jet produced at the throat was turbulent, leading to an axisymmetric region of slowly recirculating flow. For higher Reynolds numbers, this region became more disturbed and its length was reduced. The numerical predictions were confirmed by digital particle image velocimetry and used to describe the fluid dynamics mechanisms relevant to prior measurements of platelet deposition in canine blood flow (R.T. Schoephoersteret al., Atherosclerosis and Thrombosis 12:1806–1813, 1993). Actual deposition onto the wall was dependent on the wall shear stress distribution along the stenosis, increasing in areas of flow recirculation and reattachment. Platelet activation potential was analyzed under laminar and turbulent flow conditions in terms of the cumulative effect of the varying shear and elongational stresses, and the duration platelets are exposed to them along individual platelet paths. The cumulative product of shear rate and exposure time along a platelet path reached a value of 500, half the value needed for platelet activation under constant shear (J. M. Ramstacket al., Journal of Biomechanics 12: 113–125, 1979).     

Effects of disturbed flow on vascular endothelium: pathophysiological basis and clinical perspectives

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.