High Wall Shear Stress and Spatial Gradients in Vascular Pathology: A Review

Abstract

Cardiovascular pathologies such as intracranial aneurysms (IAs) and atherosclerosis preferentially localize to bifurcations and curvatures where hemodynamics are complex. While extensive knowledge about low wall shear stress (WSS) has been generated in the past, due to its strong relevance to atherogenesis, high WSS (typically >3 Pa) has emerged as a key regulator of vascular biology and pathology as well, receiving renewed interests. As reviewed here, chronic high WSS not only stimulates adaptive outward remodeling, but also contributes to saccular IA formation (at bifurcation apices or outer curves) and atherosclerotic plaque destabilization (in stenosed vessels). Recent advances in understanding IA pathogenesis have shed new light on the role of high WSS in pathological vascular remodeling. In complex geometries, high WSS can couple with significant spatial WSS gradient (WSSG). A combination of high WSS and positive WSSG has been shown to trigger aneurysm initiation. Since endothelial cells (ECs) are sensors of WSS, we have begun to elucidate EC responses to high WSS alone and in combination with WSSG. Understanding such responses will provide insight into not only aneurysm formation, but also plaque destabilization and other vascular pathologies and potentially lead to improved strategies for disease management and novel targets for pharmacological intervention.

Aortic Valve Stenosis Alters Expression of Regional Aortic Wall Shear Stress: New Insights From a 4‐Dimensional Flow Magnetic Resonance Imaging Study of 571 Subjects

“…Interestingly, these regions of increased WSS corresponded with known differences in aortopathy expression for RL‐BAV and RN‐BAV: Dilatation of the tubular AAo accompanied by aortic‐root dilatation has been associated with RL‐BAV, whereas more‐distal dilatation of the tubular AAo extending to the proximal arch with sparing of the aortic root has been associated with RN‐BAV 27. These findings therefore support the notion that increased WSS may influence outward vessel remodeling in the presence of BAV aortopathy 28. It should be noted, however, that in this cross‐sectional study, correlation of WSS in the chosen regions of interest (shown in Figure 1) did not exhibit statistically significant associations to diameter.…”

Aneurysmal Remodeling in the Circle of Willis after Carotid Occlusion in an Experimental Model

“…This creates a local hemodynamic environment with high WSS and positive WSS gradient, not dissimilar to that of bifurcation apices. 35 Based on the observed aneurysmal changes present in tortuous PComs, we speculate that high WSS and positive WSS gradient at outer curves may have triggered IEL damage 24 and aneurysmal remodeling, 19 contributing to the progressive development of tortuosity as well as segmental dilation. The relationship between tortuosity and segmental dilation and their respective etiologies should be further elucidated.…”

“…24,33 This hemodynamic condition, often associated with bifurcation apices, 34 has been recognized to independently cause de novo IA formation. 21,22,24,35 Kono et al 36 further provided clinical evidence that de novo BT aneurysms could be triggered by unphysiologically high local WSS and WSS gradient generated by proximal stenoses. As aneurysmal remodeling at the OA origin and the PCom in the experimental animals of the current study bears similar morphologic features to IA initiation at the BT (especially IEL damage), we postulate that flow-induced aneurysmal development at these other locations might also be induced by similar inciting hemodynamic insults.…”

Computational modelling of the interaction of shock waves with multiple gas-filled bubbles in a liquid

“…34 The pathologically low WSS threshold of 0.5 Pa was chosen to be at the lower-bound of estimates made by various authors, including Masuda et al 47 and Sho et al 48,49 who suggest 0.5 Pa (in rabbits), Dolan et al 7 who suggest 1 Pa, and Irace et al 50 who suggest 1.8 Pa. The pathologically high WSS threshold of 30 Pa was chosen to be at the upper-bound of estimates made by various authors, including Dolan et al 7 who suggest 10 Pa, and Dolan et al 51 who suggest up to 30 Pa. The pathologically low LWOF threshold was obtained by assuming that the innermost region of the vascular wall (i.e., the intima and media) receives oxygen solely from luminal blood 52,36 and not from the adventitial vasa vasorum.…”