The Role of Shear Stress in Atherosclerosis: Action Through Gene Expression and Inflammation?

Abstract

Atherosclerotic lesions preferentially localize near side branches or curved vessels. During the last few decades, research has been shown that low or low and oscillating shear stress is associated with plaque location. Despite ample evidence, the precise mechanism is unknown. This is mainly because of a lack of appropriate animal models. We describe two novel methods to study the hypothesis that shear stress acts through endothelial gene expression or shear stress acts through localizing of inflammation. Both literature evidence and own findings support a role for both mechanisms in atherosclerosis.

Atherosclerotic Lesion Size and Vulnerability Are Determined by Patterns of Fluid Shear Stress

“…Placement of the cast creates lowered shear stress upstream from the cast, increased shear stress in the cast, and oscillatory (ie, bidirectional, with vortices) shear stress downstream from the cast (Figure 1). 7 In the present study, we used this model to assess the effect of in vivo alterations of shear stress on the development of atherosclerosis in apolipoprotein E-deficient (apoEϪ/Ϫ) mice. Our findings reveal that atherosclerotic lesions develop under conditions of both lowered shear stress and vortices with oscillatory shear stress within 6 weeks of cast placement, whereas no lesions develop in the increased shear stress region.…”

The influence of anesthesia and fluid–structure interaction on simulated shear stress patterns in the carotid bifurcation of mice

“…Most of these publications focused on the methodology and the feasibility to calculate WSS in mice and did not link the found patterns (quantitatively or qualitatively) to biological responses or processes (Feintuch et al, 2007;Greve et al, 2006;Huo et al, 2008;Trachet et al, 2011a;Trachet et al, 2009;Van Doormaal et al, 2014). Nevertheless steady state CFD WSS patterns in the common carotid artery have been linked to the uptake of plasma macromolecules (Mohri et al, 2014) or local wall thickness (Cheng et al, 2004). Transient CFD simulations have been used to link TAWSS and OSI patterns to aneurysm progression on a within-subject basis (Ford et al, 2011;Trachet et al, 2011b).…”

Differential Responses of the Nrf2-Keap1 System to Laminar and Oscillatory Shear Stresses in Endothelial Cells

“…Constantly exposed to both biochemical and biomechanical stimuli, endothelial cells regulate bodily homeostasis in response to events such as inflammation and ischemia-reperfusion (1). A number of in vivo and in vitro studies have demonstrated that the endothelium responds to blood flow by both transcriptional and post-transcriptional mechanisms (2)(3)(4)(5). An elaborate and complex structure of arterial trees results in changes in blood flow and generates altered hemodynamic forces.…”

“…At bends and bifurcations in the aorta, where atherosclerotic lesions are prone to develop, uniform laminar flow (L-flow) 1 is disturbed by recirculation, and endothelial cells are exposed to a reduced and oscillating flow (Oflow, Refs. [2][3][4][5]. Therefore, it is believed that O-flow induces a pro-atherogenic response in the endothelium, whereas L-flow provokes anti-atherogenic gene expression.…”