Change of Direction in the Biomechanics of Atherosclerosis

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.

Understanding the fluid mechanics behind transverse wall shear stress

“…Flow splits to the arch branches were based on experimental measurements (Barakat et al, 1997) with 14.7% to the brachiocephalic trunk and 7.1% to the left subclavian artery, and 2% of the descending aortic flow to the ten intercostal arteries (see Mohamied et al, 2015). Murray׳s law (Murray, 1926) was used for further flow divisions to individual branches.…”

“…The low, oscillatory WSS theory (Caro et al, 1971, Ku et al, 1985) underlies most current investigations of lesion localisation but not all studies have supported it (Peiffer et al, 2013b). Mohamied et al (2015) showed that the multidirectionality of WSS during the cardiac cycle, characterised by the transverse wall shear stress (transWSS) metric (Peiffer et al, 2013a), may be a more significant factor. Subsequent studies have shown that high transWSS is collocated with atherosclerotic plaque prevalence in minipigs (Pedrigi et al, 2015), and is associated with transitional flow instabilities in regions prone to wall remodeling (Bozzetto et al, 2015, Ene-Iordache et al, 2015).…”

Macrophages and Dendritic Cells

“…Its direction and velocity during the cardiac cycle is complex, predictable, and includes directionality that is perpendicular to the mean bulk flow. 67 Furthermore, during systole disturbed flow is usually in the forward direction and reverses during diastole, with the location of the stagnation point (the site that momentarily has no flow) changing during the cardiac cycle. Turbulent flow has chaotic fluctuations, is irregular and unpredictable.…”

Wall shear stress in the development of in-stent restenosis revisited. A critical review of clinical data on shear stress after intracoronary stent implantation

“…Low shear stress can trigger intracellular cascades and shift phenotypic endothelial cell expression to an atherosclerotic prone state. Such endothelial cells display enhanced expression of inflammatory molecules and higher rates of apoptosis [8][9][10].…”