Wall shear stress has been implicated in the genesis of atherosclerosis because a strong correlation exists between the location of developing arterial lesions and regions where particular gradients in stress occur. Studying the behavior of endothelial cells in such regions may contribute to our understanding of the disease etiology. We report the detailed migratory history of endothelial cells subjected to large shear stress gradients caused by a surface protuberance in an in vitro model system. The history of cell migration, cell division, and cell loss from the surface was continuously monitored in confluent human umbilical vein endothelial cell monolayers for 48 hours after the onset of flow. Individual cells were tracked using time-lapse video microscopy. In contrast to a uniform laminar flow field in which cells were observed to continually rearrange their relative position with no net migration, in a disturbed flow field there was a net migration directed away from the region of high shear gradient. This organized migration pattern under disturbed flow conditions was accompanied by more than a twofold increase in cell motility. In addition, cell division increased in the vicinity of the flow separation (maximum shear stress gradient of 34 dyne/cm2 per mm) whereas cell loss was increased upstream and downstream in the regions where the shear gradient diminishes. These data suggest a steady cell proliferation-migration-loss cycle and indicate that local shear stress gradient may play a key role in the morphological remodeling of the vascular endothelium in vivo.
The analogous techniques of photoactivation of fluorescence (PAF) and fluorescence recovery after photobleaching (FRAP) have been applied previously to the study of actin dynamics in living cells. Traditionally, separate experiments estimate the mobility of actin monomer or the lifetime of actin filaments. A mathematical description of the dynamics of the actin cytoskeleton, however, predicts that the evolution of fluorescence in PAF and FRAP experiments depends simultaneously on the diffusion coefficient of actin monomer, D, the fraction of actin in filaments, FF, and the lifetime of actin filaments, tau (, Biophys. J. 69:1674-1682). Here we report the application of this mathematical model to the interpretation of PAF and FRAP experiments in subconfluent bovine aortic endothelial cells (BAECs). The following parameters apply for actin in the bulk cytoskeleton of subconfluent BAECs. PAF: D = 3.1 +/- 0.4 x 10(-8) cm2/s, FF = 0.36 +/- 0.04, tau = 7.5 +/- 2.0 min. FRAP: D = 5.8 +/- 1.2 x 10(-8) cm2/s, FF = 0.5 +/- 0.04, tau = 4.8 +/- 0.97 min. Differences in the parameters are attributed to differences in the actin derivatives employed in the two studies and not to inherent differences in the PAF and FRAP techniques. Control experiments confirm the modeling assumption that the evolution of fluorescence is dominated by the diffusion of actin monomer, and the cyclic turnover of actin filaments, but not by filament diffusion. The work establishes the dynamic state of actin in subconfluent endothelial cells and provides an improved framework for future applications of PAF and FRAP.
The non-linear elastic response of arteries implies that their mechanical properties depend strongly on blood pressure. Thus, dynamic measurements of both the diameter and pressure curves over the whole cardiac cycle are necessary to characterise properly the elastic behaviour of an artery. We propose a novel method of estimating these mechanical properties based on the analysis of the arterial diameter against pressure curves derived from ultrasonic and photoplethysmographic measurements. An ultrasonic echo tracking device has been developed that allows continuous recording of the internal diameter of peripheral arteries. It measures the diameter 300 times per second with a resolution of 2.5 microns. This system is linked to a commercially available light-plethysmograph which continuously records the finger arterial pressure (0.25 kPa accuracy). Because of the finite pulse wave velocity, the separation between the diameter and the pressure measurement sites causes a hysteresis to appear in the recorded diameter-pressure curve. Using a model based on haemodynamic considerations, the delay between the diameter variations and the finger arterial pressure is first eliminated. As the pulse wave velocity depends on the pressure, the delay is determined for each pressure value. The relationship between pressure and diameter is then described by a non-linear mathematical expression with three parameters, which best fits the recorded data. The dynamic local behaviour of the vessel is fully characterised by these parameters. Compliance, distensibility and pulse wave velocity can then be calculated at each pressure level. Thus, the mechanical behaviour of peripheral human arteries can now be characterised non-invasively over the pressure range of the whole cardiac cycle. The results obtained in vivo on human radial and brachial arteries show that a thorough analysis of the compliance-pressure curves and their modifications (curving, shift) is needed in order to compare two different vessels in a meaningful way.
The goal of this study was to investigate whether the elastic behavior of conduit arteries of humans or rats is altered as a result of concomitant hypertension. Forearm arterial cross-sectional compliance-pressure curves were determined noninvasively by means of a high precision ultrasonic echo-tracking device coupled to a photoplethysmograph (Finapres system) allowing simultaneous arterial diameter and finger blood pressure monitoring. Seventeen newly diagnosed hypertensive patients with a humeral blood pressure of 163/103 +/- 4.4/2.2 mm Hg (mean +/- SEM) and 17 age- and sex-matched normotensive controls with a humeral blood pressure of 121/77 +/- 3.2/1.9 mm Hg were included in the study. Compliance-pressure curves were also established at the carotid artery of 16-week-old anesthetized spontaneously hypertensive rats (n = 14) as well as Wistar-Kyoto normotensive animals (n = 15) using the same echo-tracking device. In these animals, intra-arterial pressure was monitored in the contralateral carotid artery. Mean blood pressures averaged 197 +/- 4 and 140 +/- 3 mm Hg in the hypertensive and normotensive rats, respectively. Despite the considerable differences in blood pressure, the diameter-pressure and cross-sectional compliance-pressure and distensibility-pressure curves were not different when hypertensive patients or animals were compared with their respective controls. These results suggest that the elastic behavior of a medium size muscular artery (radial) in humans and of an elastic artery (carotid) in rats is not necessarily altered by an increase in blood pressure.
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