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 (ReD=500) were performed with three different inlet velocity profiles; pulsatile flow simulations utilized two different flow waveforms (both with Womersley parameter=1.82, mean ReD=233), 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.
A photochromic tracer method has been used to record pulsatile flow velocity profiles simultaneously at three axial locations along a flow channel. Two major advantages of this multiple-trace method are that it enables velocity data to be acquired in an efficient non-invasive manner and that it provides a detailed description of the spatial relationship of the flow field. The latter is found to be particularly useful in the investigation of transitional type flows; for example, in describing coherent flow structures. Studies of the flow patterns in tubes with mild to moderate degrees of vessel constriction were performed using a 2.9 Hz sinusoidal flow superimposed on a steady flow (frequency parameter of 7.5; mean and modulation Reynolds numbers of 575 and 360, respectively). With mild constrictions (< 50% area reduction), isolated regions of vortical and helical structures were observed primarily during the deceleration phase of the flow cycle and in the vicinity of the reattachment point. As expected, these effects were accentuated when the constriction was asymmetric. For moderate constrictions (50%–80%), transition to turbulence was triggered just before peak flow through the breakdown of waves and streamwise vortices that were shed in the high-shear layer. During this vortex generation phase of the flow cycle, the wall shear stress fluctuated quite intensely, especially in the vicinity of the reattachment point, and its instantaneous value increased by at least a factor of eight. Such detailed descriptions of the transition to turbulence and of the spatial and temporal variation of the wall shear stress, particularly near the reattachment point, have not been previously reported for pulsatile flow through constricted tubes. The observed wall shear stress variations support a proposal by Mao & Hanratty (1986) of an interaction of the imposed flow oscillation with the turbulent fluctuations within the viscous sublayer.
Atherosclerosis develops in distinct regions of the arterial tree. Defining patterns and mechanisms of endothelial cell gene expression in different regions of normal arteries is key to understanding the initial molecular events in atherogenesis. In this study, we demonstrated that the expression of endothelial nitric-oxide synthase (eNOS), an atheroprotective gene, and its phosphorylation on Ser 1177 , a marker of activity, were lower in regions of the normal mouse aorta that are predisposed to atherosclerosis. The same expression pattern was observed in mouse strains that are both susceptible and resistant to atherosclerosis, and the topography of eNOS expression was inverse to p65, the main nuclear factor-B subunit. Modeling of disturbed and uniform laminar flow in vitro reproduced the expression patterns of eNOS and p65 that were found in vivo. Heterogeneous nuclear RNA expression and RNA polymerase II chromosome immunoprecipitation studies demonstrated that regulation of transcription contributed to increased eNOS expression in response to shear stress. In vivo, the transcription of eNOS was reduced in regions of the mouse aorta predisposed to atherosclerosis, as defined by reporter gene expression in eNOS promoter--galactosidase reporter transgenic mice. These data suggest that disturbed hemodynamic patterns found at arterial branches and curvatures uniquely modulate endothelial cell gene expression by regulating transcription , potentially explaining why these regions preferentially develop atherosclerosis when risk factors such as hypercholesterolemia are introduced.
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