scholarly journals Temporal and spatial changes in wall shear stress during atherosclerotic plaque progression in mice

2018 ◽  
Vol 5 (3) ◽  
pp. 171447 ◽  
Author(s):  
R. Xing ◽  
A. M. Moerman ◽  
Y. Ridwan ◽  
M. J. Daemen ◽  
A. F. W. van der Steen ◽  
...  

Wall shear stress (WSS) is involved in atherosclerotic plaque initiation, yet its role in plaque progression remains unclear. We aimed to study (i) the temporal and spatial changes in WSS over a growing plaque and (ii) the correlation between WSS and plaque composition, using animal-specific data in an atherosclerotic mouse model. Tapered casts were placed around the right common carotid arteries (RCCA) of ApoE −/− mice. At 5, 7 and 9 weeks after cast placement, RCCA geometry was reconstructed using contrast-enhanced micro-CT. Lumen narrowing was observed in all mice, indicating the progression of a lumen intruding plaque. Next, we determined the flow rate in the RCCA of each mouse using Doppler Ultrasound and computed WSS at all time points. Over time, as the plaque developed and further intruded into the lumen, absolute WSS significantly decreased. Finally at week 9, plaque composition was histologically characterized. The proximal part of the plaque was small and eccentric, exposed to relatively lower WSS. Close to the cast a larger and concentric plaque was present, exposed to relatively higher WSS. Lower WSS was significantly correlated to the accumulation of macrophages in the eccentric plaque. When pooling data of all animals, correlation between WSS and plaque composition was weak and no longer statistically significant. In conclusion, our data showed that in our mouse model absolute WSS strikingly decreased during disease progression, which was significantly correlated to plaque area and macrophage content. Besides, our study demonstrates the necessity to analyse individual animals and plaques when studying correlations between WSS and plaque composition.

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
E M J Hartman ◽  
A M Kok ◽  
A Hoogendoorn ◽  
F J H Gijsen ◽  
A F W Steen ◽  
...  

Abstract Introduction Local wall shear stress (WSS) metrics, high local lipid levels (as detected by near-infrared spectroscopy (NIRS)), as well as systemic lipid levels, have been individually associated with atherosclerotic disease progression. However, a possible synergistic effect remains to be elucidated. This study is the first study to combine WSS metrics with NIRS-detected local lipid content to investigate a potential synergistic effect on plaque progression in human coronary arteries. Methods The IMPACT study is a prospective, single centre study investigating the relation between atherosclerotic plaque progression and WSS in human coronary arteries. Patients with ACS treated with PCI were included. At baseline and after 1-year follow-up, patients underwent near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) imaging and intravascular doppler flow measurements of at least one non-culprit coronary artery. After one month, a CT angiography was made. CT derived centreline combined with IVUS lumen contours resulted in a 3D reconstruction of the vessel. The following WSS metrics were computed using computational fluid dynamics applying the vessel specific invasive flow measurements: time-average wall shear stress (TAWSS), relative residence time (RRT), cross-flow index, oscillatory shear index and transverse wall shear stress. Low TAWSS is known as pro atherogenic, in contrast to all the other shear stress metrics, at which a high magnitude is pro-atherogenic. The arteries were divided into 1.5mm/45° sectors. Based on NIRS-IVUS, wall thickness change over time was determined and NIRS positive sectors detected. Furthermore, per vessel the shear stress was divided into tertiles (low, intermediate, high). To investigate the synergistic effect of local lipids on shear stress related plaque growth, wall thickness change over time was related to the different shear stress metrics comparing the NIRS-positive with the NIRS-negative sectors. Results 15 non-culprit coronary arteries from the first 14 patients were analyzed (age 62±10 years old and 92.9% male). A total of 2219 sectors were studied (5.2%, N=130, NIRS-positive) for wall thickness changes. After studying all five shear stress metrics, we found for TAWSS and RRT that presence of lipids, as detected by NIRS, amplified the effect of shear stress on plaque progression (see figure). Sectors presenting with lipid-rich plaque, compared to NIRS-negative sectors, showed more progression when they were exposed to low TAWSS (p=0.07) or high RRT (p=0.012) and more regression in sectors exposed to high TAWSS (p=0.10) or low RRT (p=0.06). Delta wall thickness vs shear stress Conclusion We presented the first preliminary results of the IMPACT study, showing the synergistic effect of lipid rich plaque and shear stress on plaque progression. Therefore, intravascular lipid-rich plaque (NIRS) assessment has added value to shear stress profiling for the prediction of plaque growth, leading to improved risk stratification. Acknowledgement/Funding ERC starting grant 310457


2015 ◽  
Vol 14 (Suppl 1) ◽  
pp. S2 ◽  
Author(s):  
David S Molony ◽  
Lucas H Timmins ◽  
Olivia Y Hung ◽  
Emad Rasoul-Arzrumly ◽  
Habib Samady ◽  
...  

Author(s):  
Jin Suo ◽  
Michael McDaniel ◽  
Parham Eshtehardi ◽  
Saurabh Dhawan ◽  
Ravi Prasad Avati Nanjundappa ◽  
...  

Intravascular ultrasound (IVUS) evaluation was performed in the coronary arteries of a 45-year-old patient with stable angina during vigorous physical activity. Concurrent angiography demonstrated a mild plaque in the proximal left anterior descending artery (LAD), with obvious lumen dilatation immediately distal to the plaque. Blood velocity was measured by a catheter Doppler transducer at proximal and distal segments of the left coronary artery, and the left main artery (LM) and LAD were reconstructed using a 3D-IVUS reconstruction technique based on biplanar angiography and IVUS images, enabling simulation of the flow field in the artery employing computational fluid dynamics (CFD). Wall shear stress (WSS) and particle path lines were determined from the CFD studies. The patient returned for a follow up evaluation after 6 months, and plaque progression during this period was evaluated from the IVUS data. Results showed that low WSS, less than 5 dynes/cm2, which occurs in the region immediately distal to the plaque, correlates with localized progression of the lesion over the 6 month interval. The path line tracking computations showed that particles near the vessel surface where plaque progression was observed resided near the artery wall longer than one complete cardiac cycle, whereas in other areas particles were flushed through the region of interest rapidly. These observations in a specific individual are consistent with the hypothesis that plaque progression is related to low WSS and relatively long residence time of atherogenic blood-borne substances.


2015 ◽  
Vol 137 (6) ◽  
Author(s):  
Othmane Oulaid ◽  
Junfeng Zhang

Using a simplified two-dimensional divider-channel setup, we simulate the development process of red blood cell (RBC) flows in the entrance region of microvessels to study the wall shear stress (WSS) behaviors. Significant temporal and spatial variation in WSS is noticed. The maximum WSS magnitude and the strongest variation are observed at the channel inlet due to the close cell-wall contact. From the channel inlet, both the mean WSS and variation magnitude decrease, with a abrupt drop in the close vicinity near the inlet and then a slow relaxation over a relatively long distance; and a relative stable state with approximately constant mean and variation is established when the flow is well developed. The correlations between the WSS variation features and the cell free layer (CFL) structure are explored, and the effects of several hemodynamic parameters on the WSS variation are examined. In spite of the model limitations, the qualitative information revealed in this study could be useful for better understanding relevant processes and phenomena in the microcirculation.


2010 ◽  
Vol 132 (8) ◽  
Author(s):  
Leonie Rouleau ◽  
Monica Farcas ◽  
Jean-Claude Tardif ◽  
Rosaire Mongrain ◽  
Richard L. Leask

Endothelial cells are known to respond to hemodynamic forces. Their phenotype has been suggested to differ between atheroprone and atheroprotective regions of the vasculature, which are characterized by the local hemodynamic environment. Once an atherosclerotic plaque has formed in a vessel, the obstruction creates complex spatial gradients in wall shear stress. Endothelial cell response to wall shear stress may be linked to the stability of coronary plaques. Unfortunately, in vitro studies of the endothelial cell involvement in plaque stability have been limited by unrealistic and simplified geometries, which cannot reproduce accurately the hemodynamics created by a coronary stenosis. Hence, in an attempt to better replicate the spatial wall shear stress gradient patterns in an atherosclerotic region, a three dimensional asymmetric stenosis model was created. Human abdominal aortic endothelial cells were exposed to steady flow (Re=50, 100, and 200 and τ=4.5 dyn/cm2, 9 dyn/cm2, and 18 dyn/cm2) in idealized 50% asymmetric stenosis and straight/tubular in vitro models. Local morphological changes that occur due to magnitude, duration, and spatial gradients were quantified to identify differences in cell response. In the one dimensional flow regions, where flow is fully developed and uniform wall shear stress is observed, cells aligned in flow direction and had a spindlelike shape when compared with static controls. Morphological changes were progressive and a function of time and magnitude in these regions. Cells were more randomly oriented and had a more cobblestone shape in regions of spatial wall shear stress gradients. These regions were present, both proximal and distal, at the stenosis and on the wall opposite to the stenosis. The response of endothelial cells to spatial wall shear stress gradients both in regions of acceleration and deceleration and without flow recirculation has not been previously reported. This study shows the dependence of endothelial cell morphology on spatial wall shear stress gradients and demonstrates that care must be taken to account for altered phenotype due to geometric features. These results may help explain plaque stability, as cells in shoulder regions near an atherosclerotic plaque had a cobblestone morphology indicating that they may be more permeable to subendothelial transport and express prothrombotic factors, which would increase the risk of atherothrombosis.


Sign in / Sign up

Export Citation Format

Share Document