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High Fluid Shear Stress and Spatial Shear Stress Gradients Affect Endothelial Proliferation, Survival, and Alignment

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Abstract

Cerebral aneurysms develop near bifurcation apices, where complex hemodynamics occur: Flow impinges on the apex, accelerates into branches, then slows again distally, creating high wall shear stress (WSS) and positive and negative spatial gradients in WSS (WSSG). Endothelial responses to these kinds of high WSS hemodynamic environments are not well characterized. We examined endothelial cells (ECs) under elevated WSS and positive and negative WSSG using a flow chamber with constant-height channels to create regions of uniform WSS and converging and diverging channels to create positive and negative WSSG, respectively. Cultured bovine aortic ECs were subjected to 3.5 and 28.4 Pa with and without WSSG for 24 and 36 h. High WSS inhibited EC alignment to flow, increased EC proliferation assessed by bromodeoxyuridine incorporation, and increased apoptosis determined by terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling. These responses to high WSS were either accentuated or ameliorated by WSSG: Positive WSSG (+980 Pa/m) inhibited alignment and stimulated proliferation and apoptosis, whereas negative WSSG (−1120 Pa/m) promoted alignment and suppressed proliferation and apoptosis. These results demonstrate that ECs discriminate between positive and negative WSSG under high WSS conditions. EC responses to positive WSSG may contribute to pathogenic remodeling that occurs at bifurcations preceding aneurysm formation.

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Acknowledgments

We thank Eleni Metaxa for contributions to chamber design and stimulating discussions, Robert Baier for critical advice on biocompatible materials, Scott Woodward for technical assistance in chamber design, Nicholas Liaw for stimulating discussions, and Jianping Xiang for assistance with CFD. We also acknowledge the assistance of Wade Sigurdson and the Confocal Microscope and Flow Cytometry Core Facility at the University of Buffalo. This work was supported by the NIH grant R01NS064592 (H.M.) and the American Society for Quality (J.D.).

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Authors and Affiliations

  1. Toshiba Stroke Research Center, State University of New York at Buffalo, Buffalo, NY, 14214, USA

    Jennifer M. Dolan, Hui Meng, Sukhjinder Singh & John Kolega

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

    Jennifer M. Dolan & Hui Meng

  3. Department of Pathology & Anatomical Sciences, School of Medicine & Biomedical Sciences, State University of New York at Buffalo, 206A Farber Hall, 3435 Main Street, Buffalo, NY, 14214, USA

    Jennifer M. Dolan & John Kolega

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

    Hui Meng & Sukhjinder Singh

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

    Hui Meng

  6. Department of Pediatrics, State University of New York at Buffalo, Buffalo, NY, 14214, USA

    Rocco Paluch

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  1. Jennifer M. Dolan
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  5. John Kolega
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Correspondence to John Kolega.

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Associate Editor K. A. Athanasiou oversaw the review of this article.

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Dolan, J.M., Meng, H., Singh, S. et al. High Fluid Shear Stress and Spatial Shear Stress Gradients Affect Endothelial Proliferation, Survival, and Alignment. Ann Biomed Eng 39, 1620–1631 (2011). https://doi.org/10.1007/s10439-011-0267-8

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