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

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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.

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Acknowledgments

We thank Nicholas Liaw for critical review of the manuscript and assistance with figures, and Chris Martensen for assistance with figures and references. This work was supported by NIH grant R01NS064592 (awarded to H.M.).

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  1. Toshiba Stroke and Vascular Research Center, Clinical and Translational Research Center of the University at Buffalo, State University of New York, 875 Ellicott St., Buffalo, NY, 14203, USA

    Jennifer M. Dolan, John Kolega & Hui Meng

  2. Department of Mechanical and Aerospace Engineering, University at Buffalo, State University of New York, Buffalo, NY, 14214, USA

    Hui Meng

  3. Neuroscience Program, University at Buffalo, State University of New York, Buffalo, NY, 14214, USA

    Jennifer M. Dolan, John Kolega & Hui Meng

  4. Department of Pathology and Anatomical Sciences, University at Buffalo, State University of New York, Buffalo, NY, 14214, USA

    Jennifer M. Dolan & John Kolega

  5. Department of Neurosurgery, University at Buffalo, State University of New York, Buffalo, NY, 14214, USA

    Hui Meng

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  1. Jennifer M. Dolan
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Correspondence to Hui Meng.

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Associate Editor Seungik Baek oversaw the review of this article.

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Dolan, J.M., Kolega, J. & Meng, H. High Wall Shear Stress and Spatial Gradients in Vascular Pathology: A Review. Ann Biomed Eng 41, 1411–1427 (2013). https://doi.org/10.1007/s10439-012-0695-0

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