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Change of direction in the biomechanics of atherosclerosis.

Mohamied Y, Rowland EM, Bailey EL, Sherwin SJ, Schwartz MA, Weinberg PD - Ann Biomed Eng (2014)

Bottom Line: Lesion prevalence correlated positively, strongly and significantly with transWSS at both ages.Correlations of lesion prevalence with the other shear metrics were not significant or were significantly lower than those obtained for transWSS.The finding that oscillatory flow has pro-inflammatory effects when acting perpendicularly to the long axis of EC but anti-inflammatory effects when acting parallel to it may explain the stronger correlation of lesion prevalence with transWSS than with the OSI.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioengineering, Imperial College London, London, SW7 2AZ, UK.

ABSTRACT
The non-uniform distribution of atherosclerosis within the arterial system has been attributed to pro-atherogenic influences of low, oscillatory haemodynamic wall shear stress (WSS) on endothelial cells (EC). This theory is challenged by the changes in lesion location that occur with age in human and rabbit aortas. Furthermore, a number of point-wise comparisons of lesion prevalence and WSS have failed to support it. Here we investigate the hypothesis that multidirectional flow-characterized as the average magnitude of WSS components acting transversely to the mean vector (transWSS)-plays a key role. Maps of lesion prevalence around aortic branch ostia in immature and mature rabbits were compared with equivalent maps of time average WSS, the OSI (an index characterizing oscillatory flow) and transWSS, obtained from computational simulations; Spearman's rank correlation coefficients were calculated for aggregated data and 95% confidence intervals were obtained by bootstrapping methods. Lesion prevalence correlated positively, strongly and significantly with transWSS at both ages. Correlations of lesion prevalence with the other shear metrics were not significant or were significantly lower than those obtained for transWSS. No correlation supported the low, oscillatory WSS theory. The data are consistent with the view that multidirectional near-wall flow is highly pro-atherogenic. Effects of multidirectional flow on EC, and methods for investigating them, are reviewed. The finding that oscillatory flow has pro-inflammatory effects when acting perpendicularly to the long axis of EC but anti-inflammatory effects when acting parallel to it may explain the stronger correlation of lesion prevalence with transWSS than with the OSI.

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Mean correlation coefficients (with 95% confidence intervals) for the relation between lesion prevalence and the three WSS metrics shown in Figs. 2 and 3
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Fig4: Mean correlation coefficients (with 95% confidence intervals) for the relation between lesion prevalence and the three WSS metrics shown in Figs. 2 and 3

Mentions: Figure 4 shows the correlation coefficients and associated confidence intervals for the relation between lesion prevalence and the three shear metrics at both ages. Considering first the time average WSS, there was no significant correlation in the mature animals. There was a positive correlation in the immature animals. The correlation in the younger group was significant in this study despite being only borderline in our earlier investigation because the new statistical methods have somewhat greater power; however, the value of the coefficient was low. There was no significant correlation between lesion prevalence and the OSI for the mature animals, and a significant inverse correlation—albeit with another low coefficient—for the immature animals. TransWSS correlated significantly with lesion prevalence in mature animals, unlike the other two metrics. It also correlated significantly in the immature animals, and significantly more strongly than the other two metrics. At both ages, the correlation coefficients for the transWSS were positive and approximately three times those observed for the other metrics.Figure 4


Change of direction in the biomechanics of atherosclerosis.

Mohamied Y, Rowland EM, Bailey EL, Sherwin SJ, Schwartz MA, Weinberg PD - Ann Biomed Eng (2014)

Mean correlation coefficients (with 95% confidence intervals) for the relation between lesion prevalence and the three WSS metrics shown in Figs. 2 and 3
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4286626&req=5

Fig4: Mean correlation coefficients (with 95% confidence intervals) for the relation between lesion prevalence and the three WSS metrics shown in Figs. 2 and 3
Mentions: Figure 4 shows the correlation coefficients and associated confidence intervals for the relation between lesion prevalence and the three shear metrics at both ages. Considering first the time average WSS, there was no significant correlation in the mature animals. There was a positive correlation in the immature animals. The correlation in the younger group was significant in this study despite being only borderline in our earlier investigation because the new statistical methods have somewhat greater power; however, the value of the coefficient was low. There was no significant correlation between lesion prevalence and the OSI for the mature animals, and a significant inverse correlation—albeit with another low coefficient—for the immature animals. TransWSS correlated significantly with lesion prevalence in mature animals, unlike the other two metrics. It also correlated significantly in the immature animals, and significantly more strongly than the other two metrics. At both ages, the correlation coefficients for the transWSS were positive and approximately three times those observed for the other metrics.Figure 4

Bottom Line: Lesion prevalence correlated positively, strongly and significantly with transWSS at both ages.Correlations of lesion prevalence with the other shear metrics were not significant or were significantly lower than those obtained for transWSS.The finding that oscillatory flow has pro-inflammatory effects when acting perpendicularly to the long axis of EC but anti-inflammatory effects when acting parallel to it may explain the stronger correlation of lesion prevalence with transWSS than with the OSI.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioengineering, Imperial College London, London, SW7 2AZ, UK.

ABSTRACT
The non-uniform distribution of atherosclerosis within the arterial system has been attributed to pro-atherogenic influences of low, oscillatory haemodynamic wall shear stress (WSS) on endothelial cells (EC). This theory is challenged by the changes in lesion location that occur with age in human and rabbit aortas. Furthermore, a number of point-wise comparisons of lesion prevalence and WSS have failed to support it. Here we investigate the hypothesis that multidirectional flow-characterized as the average magnitude of WSS components acting transversely to the mean vector (transWSS)-plays a key role. Maps of lesion prevalence around aortic branch ostia in immature and mature rabbits were compared with equivalent maps of time average WSS, the OSI (an index characterizing oscillatory flow) and transWSS, obtained from computational simulations; Spearman's rank correlation coefficients were calculated for aggregated data and 95% confidence intervals were obtained by bootstrapping methods. Lesion prevalence correlated positively, strongly and significantly with transWSS at both ages. Correlations of lesion prevalence with the other shear metrics were not significant or were significantly lower than those obtained for transWSS. No correlation supported the low, oscillatory WSS theory. The data are consistent with the view that multidirectional near-wall flow is highly pro-atherogenic. Effects of multidirectional flow on EC, and methods for investigating them, are reviewed. The finding that oscillatory flow has pro-inflammatory effects when acting perpendicularly to the long axis of EC but anti-inflammatory effects when acting parallel to it may explain the stronger correlation of lesion prevalence with transWSS than with the OSI.

Show MeSH
Related in: MedlinePlus