Force exerted on maxillary anterior teeth in mandibular unilateral and bilateral distal extension partial edentulous situation.

The purpose of this study was to determine the influence of mandibular unilateral and bilateral distal extension partial edentulous situation and the use of removable partial dental prostheses on the force exerted on maxillary anterior teeth. A commercially available jaw model with exchangeable teeth was used. Seven experimental conditions of mandibular distal extension edentulous situation were prepared and a distal extension removable partial dental prosthesis to replace missing posterior teeth was fabricated. The occlusal force was measured by inserting an occlusal force measuring film between the maxillary and mandibular teeth of the model. An occlusal load was applied and the forces and ratios were compared using the Kruskal-Wallis test and the Mann-Whitney U test (p < 0.05). As a result, the force exerted on the maxillary anterior teeth increased significantly as the number of remaining teeth decreased in unilateral and bilateral edentulous situation. The force exerted on the maxillary anterior teeth decreased significantly with use of a removable partial dental prosthesis. It is concluded that when the number of remaining teeth decreases in mandibular unilateral and bilateral distal extension partial edentulous situation, the burden on the maxillary anterior teeth increases. Our findings suggest that for patients with mandibular distal extension partial edentulous situation, using a removable partial dental prosthesis is effective in preserving the remaining teeth by reducing excessive force.

Clinical Measurements of Force Exerted on Anterior Teeth in Partial Edentulous Distal Extension.

PURPOSE: To determine the influence of partial edentulous distal extension and the use of removable partial dental prostheses in partially edentulous areas on the force exerted on the anterior teeth. MATERIALS AND METHODS: A total of 83 volunteer patients participated in this study. The occlusal force was measured using an occlusal force measuring sheet in the patient's mouth. The occlusal forces and ratios were compared using the Wilcoxon signed-rank test (P < .05). RESULTS: The force exerted on the anterior teeth increased significantly as the number of remaining teeth decreased in an edentulous distal extension. The force exerted on the anterior teeth decreased significantly with the use of a removable partial dental prosthesis. CONCLUSIONS: In a clinical setting, when the number of remaining teeth in a partial edentulous distal extension decreases, the burden on the anterior teeth increases. Our findings suggest that, for patients with partial edentulous distal extension, using a removable partial dental prosthesis is effective in preserving the residual anterior teeth by reducing excessive force.

Clinical measurement of force exerted on anterior teeth in partial edentulous distal extension.

PURPOSE: The aim of this clinical study was to determine the influence of partial edentulous distal extension and the use of removable partial dental prostheses in partially edentulous areas on the force exerted on the anterior teeth. MATERIALS AND METHODS: Eighty-three volunteer patients participated in this study. The occlusal force was measured by using an occlusal force measuring sheet in the patient's mouth. The occlusal forces and ratios were compared with the Wilcoxon signed-rank test (p < 0.05). RESULTS: The force exerted on the anterior teeth increased significantly as the number of remaining teeth decreased in an edentulous distal extension. The force exerted on the anterior teeth decreased significantly with the use of a removable partial dental prosthesis. CONCLUSION: When the number of remaining teeth decreases in a partial edentulous distal extension, the burden on the anterior teeth increases in a clinical setting. Our findings suggest that, for patients with partial edentulous distal extension, using a removable partial dental prosthesis is effective in preserving the residual anterior teeth by reducing excessive force. Int J Prosthodont 2023. doi: 10.11607/ijp.8281.

Flow-dependent accumulation of LDL in co-cultures of endothelial and smooth muscle cells in the presence of filtration flow through the cell layer.

To elucidate the roles of blood flow and transmural filtration flow in localized LDL accumulation in vascular walls, we studied the effects of flow velocity on LDL concentration at the cell surface and LDL uptake by co-cultures of vascular endothelial cells (ECs) and smooth muscle cells using a parallel-plate flow cell with or without filtration flow. Co-cultures were prepared on porous membranes. In the presence of filtration flow through the cell layer, the LDL concentration at the cell surface increased when the perfusion velocity was decreased (shear stress was decreased from 1.5 to 0.2 Pa). In the absence of filtration flow, LDL concentration remained unchanged despite changes in flow velocity. LDL uptake by the cells was proportional to its surface concentration that varied inversely with flow velocity. Therefore, in the presence of filtration flow, LDL accumulation was greater under conditions of low shear stress (0.2 Pa) than with high shear stress (1.5 Pa). In contrast, in the absence of filtration flow, LDL uptake was almost proportional to the magnitude of shear stress. These results suggest that shear stress-induced biological responses of ECs and transmural filtration flow, both play important roles in localized LDL accumulation in vascular walls.

Effect of serum concentration on adhesion of monocytic THP-1 cells onto cultured EC monolayer and EC-SMC co-culture.

BACKGROUND: The adhesion of monocytes to the endothelium following accumulation of low-density lipoprotein (LDL) in subendothelial spaces is an important step in the development of intimal hyperplasia in arterially implanted vein grafts and atherosclerosis in both animals and humans. However, it is not well known how serum factors affect the adhesion of monocytes. METHODS: We have studied the effect of fetal calf serum (FCS), which we considered a source of LDL, on the adhesion of monocytes to endothelial cells (ECs) by using human monocytic THP-1 cells and both a monolayer of cultured bovine aortic endothelial cells (EC monoculture) and a co-culture with bovine aortic smooth muscle cells (EC-SMC co-culture). RESULTS: It was found that the addition of FCS to the medium greatly affected the adhesion of THP-1 cells, and the higher the concentration of FCS in the medium, the greater the adhesion of THP-1 cells to endothelial cells. Adhesion of THP-1 cells to an EC-SMC co-culture was approximately twofold greater than that to an EC monoculture, and after adhering to endothelial cells, many THP-1 cells transmigrated into the layer of smooth muscle cells. CONCLUSION: The results suggest that the elevation of the LDL (cholesterol) level in blood provides a favorable condition for the development of intimal hyperplasia and atherosclerosis by promoting the adhesion of monocytes to the endothelium and their subsequent migration into subendothelial spaces.

Flow patterns and preferred sites of intimal thickening in diameter-mismatched vein graft interpositions.

BACKGROUND: It is suspected that blood flow and flow-induced shear stress play an important role in the pathogenesis and localization of intimal hyperplasia in anastomosed vessels. However, experimental data that demonstrate the correlation between the flow and the sites of intimal thickening obtained in the same vessel are scarce. For this reason, we have studied the relationship between the flow and precise locations of wall thickening specific to the particular vessel by performing diameter-mismatched vein graft interpositions. This method created more flow disturbances than those found in our previous study, which was carried out by dividing an artery and simply suturing its ends back to their original positions. METHODS: In the current study, grafting procedures consisting of 26 saphenous vein interpositions and 10 jugular vein interpositions were carried out on the femoral arteries of 22 adult mongrel dogs. The vessels were harvested at 3 months after operation, perfusion-fixed, and rendered transparent. The precise location and the size of intimal thickening and characteristics of the flow, such as flow patterns, distributions of fluid velocity, and wall shear stress, were studied in detail by means of flow visualization and cinemicrographic techniques. RESULTS: It was found that the diameters of interposed saphenous vein grafts, which were about one-half the diameter of host arteries, increased drastically and became almost the same as those of the host arteries. Intimal thickening was found distal to the distal anastomotic junction in smaller diameter saphenous vein-interposed vessels and distal to the proximal anastomotic junction in larger diameter jugular vein-interposed vessels. In both cases, flow was disturbed with the formation of a slow recirculation flow due to a sudden enlargement of vessel diameter caused by a mismatch of vessel diameters at the anastomotic junction and at the location where the wall shear stress was low. CONCLUSIONS: The results suggest that the key hemodynamic factors involved in the localization of intimal thickening are the low velocity of flowing blood and the resultant low shear stress acting on the vessel wall.

Difference in lower critical solution temperature behavior between random copolymers and a homopolymer having solvatophilic and solvatophobic structures in an ionic liquid.

The solubility and phase behavior of poly(benzyl methacrylate) (PBzMA) and poly(styrene-co-methyl methacrylate) (P(St-co-MMA)) in a hydrophobic ionic liquid, 1-ethyl-3-methylimidazolium bis(trifluoromethane sulfone)imide ([C(2)mim][NTf(2)]), have been explored as a function of temperature. Although both polymers have solvatophobic phenyl groups and solvatophilic methacrylate groups in the structure, their distribution on the polymer chains is quite different. In PBzMA, both structures are incorporated in each monomer unit, whereas in P(St-co-MMA)s the distribution is statistically determined by the monomer reactivity ratio of St and MMA. Both polymer solutions in [C(2)mim][NTf(2)] become turbid with an increase in temperature (lower critical solution temperature (LCST) behavior). The turbidity change occurs sharply at 100 degrees C for PBzMA, whereas it is sluggish for P(St-co-MMA)s. The LCST-type phase-separation temperature for P(St-co-MMA)s decreases with an increase of the St composition. The sluggish phase separation for P(St-co-MMA)s has been explained in terms of the presence of the MMA sequences along the polymer chain, which inhibits the St aggregation to a certain extent. The dynamic light scattering (DLS) measurements for PBzMA reveal that the hydrodynamic radius of PBzMA suddenly changes at 100 degrees C; below this temperature, no aggregation is observed. This result strongly implies that the coil-to-collapse transition is of the first-order type. It has been demonstrated that the LCST-type phase separation of the polymers in an ionic liquid is greatly affected by the distribution of the solvatophilic and solvatophobic groups on the polymer chains.

Improved arterial wall model by coculturing vascular endothelial and smooth muscle cells.

We have constructed an in vitro arterial wall model by coculturing bovine arterial endothelial cells (ECs) and smooth muscle cells (SMCs). When ECs were seeded directly over SMCs and cocultured in an ordinary culture medium, ECs grew sparsely and did not form a confluent monolayer. Addition of ascorbic acid to the culture medium at concentrations greater than 50 mug/ml increased the production of type IV collagen by the SMCs, and ECs formed a confluent monolayer covering the entire surface of SMCs. Histological studies showed that the thickness of the cell layer composed of ECs and SMCs increased with increasing duration of coculture. This arterial wall model, prepared by our method, may serve as a simple and good in vitro model to study the effects of factors such as biological chemicals and shear stress on cell proliferation and other physiological functions of arterial walls.

Reactive oxygen species mediate shear stress-induced fluid-phase endocytosis in vascular endothelial cells.

To elucidate the role of shear stress in fluid-phase endocytosis of vascular endothelial cells (EC), we used a rotating-disk shearing apparatus to investigate the effects of shear stress on the uptake of lucifer yellow (LY) by cultured bovine aortic endothelial cells (BAEC). Exposure of EC to shear stress (area-mean value of 10 dynes/cm2) caused an increase in LY uptake that was abrogated by the antioxidant, N-acetyl-L-cysteine (NAC), the NADPH oxidase inhibitor, acetovanillone, and two inhibitors of protein kinase C (PKC), calphostin C and GF109203X. These results suggest that fluid-phase endocytosis is regulated by both reactive oxygen species (ROS) and PKC. Shear stress increased both ROS production and PKC activity in EC, and the increase in ROS was unaffected by calphostin C or GF109203X, whereas the activation of PKC was reduced by NAC and acetovanillone. We conclude that shear stress-induced increase in fluid-phase endocytosis is mediated via ROS generation followed by PKC activation in EC.

Flow Behavior and Distribution of Embolus-Model Particles at the Terminal Bifurcation of the Human Internal Carotid Artery.

BACKGROUND: To investigate the possible role of fluid mechanical factors in thromboembolism that occurs at a high rate in the human middle cerebral artery (MCA). METHODS: Isolated transparent cerebral arterial trees containing the terminal bifurcation of the internal carotid artery (ICA), where the ICA bifurcated into the MCA and the anterior cerebral artery, were prepared from human cadavers. The flow behavior and distribution of embolus-model polystyrene particles in dilute suspensions at the bifurcation were studied in detail by means of flow visualization and high-speed cinemicrographic techniques. RESULTS: Large particles in suspensions flowing through the ICA migrated radially away from the vessel wall toward the axis of the ICA. It became more remarkable by increasing the flow rate in the ICA (Q0), flow rate ratio of Q1 to Q0 (MCA/ICA), and particle diameter. As a result, redistribution of particles flowing in the ICA occurred at the bifurcation. The particles >1 mm in diameter (≈1/4 of vessel diameter) selectively entered the MCA, even when the flow rate ratio of Q1 to Q0 was decreased to as low as 0.34. In contrast, the particles whose diameters were <0.3 mm (≈1/10 of vessel diameter) and that did not show radial migration entered the MCA at the same rate as the flow rate ratio of Q1 to Q0. CONCLUSIONS: Due to the flow-dependent migration of particles away from the vessel wall toward the axis of the ICA, large particles selectively enter the MCA to which the core flow of the ICA is generally directed. This might explain why the incidence of thromboembolism is higher in the MCA than in the anterior cerebral artery in humans.

Effects of a ventricular untwisting on intraventricular diastolic flow and color M-mode Doppler echocardiograms.

Intraventricular hemodynamics during diastole was numerically analyzed in order to investigate effects of a ventricular untwisting on flow and a pattern of a color M-mode Doppler echocardiogram. Results showed that the ventricular untwisting affected secondary flows by inducing spiral flows in the ventricular cavity especially in the apical region. On the other hand, flows in the long-axis plane were not affected. Timing of formation, size and growing manner of the annular vortex were almost the same regardless of the presence of the ventricular untwisting; the vortex firstly arose in the base region, expanded towards the apex and eventually occupied the upper half of the ventricular cavity. A pattern of a color M-mode Doppler echocardiogram, that is, a spatiotemporal map of velocity along the long axis, was topologically the same as quantitatively confirmed by comparison of propagation velocity (0.43 m/s and 0.42 m/s for the case without and with the ventricular untwisting, respectively). These results suggested that this technique can exclusively capture flow dynamics produced by ventricular expansion with little influence of the ventricular untwisting. Therefore, we concluded that this is advantageous for assessing a left ventricular diastolic function.

Cellular growth under hydrostatic pressure using bovine aortic EC-SMC co-cultured ePTFE vascular graft.

High blood pressure (hypertension) is implicated in the development of atherosclerosis. Blood vessels are constantly subjected to stretch due to blood pressure and changes in stretch usually instigate adaptive vascular remodeling, including abnormal growth and proliferation of vascular smooth muscle cells (VSMCs) as well as extracellular matrix (ECM). In this experiment, we used bovine aortic endothelial cells and smooth muscle cells (EC-SMC) co-cultured ePTFE vascular grafts subjected to normal atmospheric pressure (as a control), and 100 mmHg hydrostatic pressure for 7 d. The increase of cell layer thickness was observed. When measured, the cell layer thickness increased by 116.2%. The increase of collagen (Type IV) synthesis was also observed in the immunohistochemistry assay. When stained with toluidine blue, the cells showed metachromatic phenomenon.

Roles of protein kinase C delta in the accumulation of P53 and the induction of apoptosis in H2O2-treated bovine endothelial cells.

To clarify the signaling pathways of oxidative stress-induced apoptosis in bovine aortic endothelial cells (BAEC), we treated cells with 1 mM H2O2 and investigated the roles of protein kinase C delta (PKC delta) and Ca2+ in the accumulation of p53 associated with apoptosis. The treatment of cells with H2O2 caused the accumulation of p53, which was inhibited by rottlerin (a PKC delta inhibitor) but not by BAPTA-AM (an intracellular Ca2+ chelator). PKC delta itself was activated through the phosphorylation at tyrosine residues. H2O2 induced the release of cytochrome c and the activation of caspases 3 and 9, and these apoptotic signals were inhibited by rottlerin and BAPTA-AM. These results suggest that PKC delta contributes to the accumulation of p53 and that Ca2+ plays a role in downstream signals of p53 leading to apoptosis in H2O2-treated BAEC.

Prediction of LDL concentration at the luminal surface of a vascular endothelium.

To find out whether concentration polarization of low-density lipoprotein (LDL) occurs at the surface of a vascular endothelium or not, transport of LDL in flowing blood to an water-permeable endothelium was studied theoretically by means of CFD. Calculations were carried out for an endothelium exposed to a Couette flow by assuming that the surface geometry of the endothelium could be expressed by a cosine function. Two typical cases were considered for the permeability of endothelium to water; one was uniform permeability everywhere in the endothelium, and the other was uneven permeability which was augmented at the intercellular junction. It was found that, in both cases, the surface concentration of LDL increased in going distally from the entrance, taking locally high and low values at the valleys and hills of the endothelium, respectively, and the variation was larger in the case of endothelium with uneven permeability. These results clearly showed that concentration polarization of LDL which might affect the uptake of LDL by the arterial wall certainly occurs at the surface of the endothelium even if the flow is disturbed microscopically by the uneven surface of the endothelium.

Flow patterns and preferred sites of atherosclerotic lesions in the human aorta - I. Aortic arch.

OBJECTIVES: To elucidate the role of fluid mechanical factors in the localized genesis and development of atherosclerotic lesions in man. METHODS: Flow patterns and preferred sites of atherosclerotic lesions in the human aortic arch were studied in detail using isolated transparent aortic trees prepared from humans postmortem and by means of flow visualization of tracer polystyrene microspheres, using cinemicrographic techniques. RESULTS: Under the condition of steady flow that simulated mid-systole, the flow in the aortic arch consisted of three major components; (i) a straight flow to the brachio-cephalic artery located close to the right dorsal wall of the ascending aorta; (ii) a quasi-parallel undisturbed flow located close to the common median plane of the aortic arch and its side branches, and (iii) a clockwise slow, spiral secondary flow located dominantly near the left ventral wall of the aortic arch. Thus, looking down the aorta from its origin, the flow in the aortic arch appeared as a single helical flow revolving in a clockwise direction. CONCLUSIONS: Atherosclerotic lesions were found mainly in regions of low wall shear stress such as the proximal lip of the orifice of each side branch where a slow recirculation flow formed, and the left ventral wall of the aortic arch where a slow spiral secondary flow formed.

Flow patterns and preferred sites of atherosclerotic lesions in the human aorta - II. Abdominal aorta.

OBJECTIVE: As in Part I, to elucidate the role of fluid mechanical factors in the localized genesis and development of atherosclerotic lesions in man, here in the abdominal aorta. METHODS: Flow patterns and preferred sites of atherosclerotic lesions in the aorta were studied in detail using the same isolated transparent aortic trees prepared from humans postmortem and the flow visualization and cinemicrographic techniques as in Part I. RESULTS: Under steady flow simulating mid-systole, the flow was found to be disturbed at the aorto-celiac and aorto-superior mesenteric artery junctions by the formation of complex secondary and adverse flows along the lateral and posterior walls of the abdominal aorta. More complex secondary and adverse flows formed at the branching sites of the left and right renal arteries. Furthermore, considerable interactions occurred between the secondary and adverse flows formed at the branching sites of the above four arteries, resulting in the formation of a large and long recirculation zone along the lateral and posterior walls of the abdominal aorta corresponding to these branches. The velocity profile was almost flattened throughout the entire length of the descending aorta. CONCLUSIONS: Atherosclerotic lesions were found mainly at the posterior and lateral walls of the abdominal aorta where slow adverse and recirculation flows formed and where wall shear stress was low.

Flow patterns and velocity distributions in the human vertebrobasilar arterial system. Laboratory investigation.

OBJECT: The authors conducted a study to elucidate the relationship between the flow patterns and the formation of aneurysms at the bifurcation of the basilar artery (BA). METHODS: Six isolated, transparent vertebrobasilar arterial systems were prepared from humans postmortem, and flow patterns and velocity distributions were studied in detail using flow visualization and cinemicrographic techniques. RESULTS: The authors found that if the diameters of 2 vertebral arteries (VAs) were nearly equal and they formed a symmetrical inverted Y-shaped junction with the BA, the BA flow was also symmetrical. The fluid elements that flowed into the BA from 2 VAs traveled almost parallel to the vessel wall of the BA without mixing with each other, and then they flowed out through ipsilateral superior cerebellar and posterior cerebral arteries. In contrast to this, if the diameters of 2 VAs were very different or the BA was badly bent, the BA flow was disturbed as a result of the formation of swirling and secondary flows. The approaching velocity profile at the BA's terminal bifurcation was flattened if the inverted Y-junction was symmetrical, and it was sharpened if the junction was asymmetrical. Thus, in the latter case, fluid elements impinged on the vessel wall around the flow divider of the bifurcation with much larger velocities and, hence, larger kinetic energy, compared with the case of a symmetrical inverted Y-junction, exerting high fluid pressures, wall shear stresses, and wall tensions on the vessel wall there. CONCLUSIONS: The symmetrical structure of the inverted Y-junction in a normal vertebrobasilar arterial system provides a flattened approaching velocity profile at the terminal bifurcation of the BA, lowering the hemodynamic stresses (pressure, tension, and shear stress) exerted on the wall of the bifurcation. This may account for the relatively low incidence of aneurysm formation at this site.

Flow patterns and distributions of fluid velocity and wall shear stress in the human internal carotid and middle cerebral arteries.

BACKGROUND: The aim of this study is to elucidate the relationship between the flow patterns and the preferred sites of the development of atherosclerotic lesions and cerebral aneurysms in the human ICA and MCA. METHODS: Five isolated transparent arterial trees containing the ICA and MCA with a sufficient length of the carotid siphon were prepared from humans postmortem, and flow patterns and distributions of fluid velocity and wall shear stress in these vessels were studied in detail using flow visualization and high-speed cinemicrographic techniques. RESULTS: In the carotid siphon that contained several acute bends, due to the impingement and deflection of the flow at the bends, a strong and complex helicoidal flow formed. As a result, the approaching velocity profile was flattened at the terminal bifurcation of the ICA, but it was sharpened at the first bifurcation of the MCA. Thus, at this latter bifurcation, fluid elements impinged on the vessel wall around the flow divider with much larger velocity than that at the preceding terminal bifurcation of the ICA. Throughout the entire arterial tree, atherosclerotic lesions were found almost exclusively in regions of low wall shear stress. CONCLUSIONS: The carotid siphon provided a flattened approaching velocity profile at the terminal bifurcation of the ICA, making the hemodynamic stresses (pressure, tension, and shear stress) exerted on the vessel wall much lower than that at the bifurcation of the MCA where the approaching velocity profile was sharpened. This may account for the relatively low incidence of aneurysm formation at this site.

Effect of a disturbed flow on proliferation of the cells of a hybrid vascular graft.

Atherosclerotic lesions and intimal hyperplasia develop preferentially in regions where blood flow is disturbed by the formation of secondary and recirculation flows. Hence, to investigate the mechanism of the localization of these vascular diseases, we constructed a sudden tubular expansion consisting of a 0.92 mm i.d. upstream tube and a 3.0 mm i.d. hybrid vascular graft, and by recirculating a cell culture medium through it in steady flow for 7 days, we tested the effect of a disturbed flow (an annular vortex) on proliferation of smooth muscle cells (SMC) of the hybrid graft. It was found that the thickness of the cell layer that was considered a measure of the proliferation of SMC underlying the endothelial cells was greatest around the reattachment point (the toe of the annular vortex) where the flow was the slowest and the wall shear stress was the lowest. The thickening of the cell layer also occurred around the stagnation point located at the origin of the expansion but was much less than that around the reattachment point. The cell layer was the thinnest in the middle portion of the vortex where the flow was the fastest and wall shear stress was the highest. These results indicated that a disturbed flow provides favorable conditions for the proliferation of SMC in regions where the flow is very slow and wall shear stress is very low. This may explain, in part, why intimal hyperplasia and atherosclerotic lesions develop preferentially in regions of slow flow.

Effect of a disturbed flow on adhesion of monocytes to a model of an arterial wall.

Monocytes are involved in the pathogenesis and localization of intimal hyperplasia and atherosclerosis in regions of disturbed flow in man. Hence, to investigate the mechanism of the localization of these vascular diseases, we created a state of disturbed flow distal to a 0.92 mm into 3.0 mm sudden tubular expansion consisting of a stainless steel upstream tube and a hybrid vascular graft by recirculating a cell culture medium through it in steady flow. Then by introducing fluorescence-labeled human blood monocytes (THP-1 cells) into the medium, we tested the effect of a disturbed flow (an annular vortex) on adhesion of monocytes to the endothelium of the hybrid graft. It was found that adhesion and invasion of THP-1 cells to the endothelium were the highest around the reattachment point (the toe of the annular vortex) where the flow was the slowest and wall shear stress was the lowest. They were the lowest at a location between the step of the tubular expansion and the reattachment point that was close to the vortex center where the flow was the fastest and wall shear stress was the highest. A similar distribution was also obtained with 20 nm diameter polystyrene microspheres used as a model of low-density lipoproteins (LDL). These results indicated that a disturbed flow itself provided favorable conditions for the adhesion of monocytes and LDL to the endothelium in regions of very slow flow, and hence low wall shear stress, by allowing them to make contact and interact with endothelial cells for a long time. This may explain, in part, why intimal hyperplasia and atherosclerotic lesions develop preferentially in regions of very slow flow.