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Correlation Between Local Hemodynamics and Lesion Distribution in a Novel Aortic Regurgitation Murine Model of Atherosclerosis

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Abstract

Following surgical induction of aortic valve regurgitation (AR), extensive atherosclerotic plaque development along the descending thoracic and abdominal aorta of Ldlr −/− mice has been reported, with distinct spatial distributions suggestive of a strong local hemodynamic influence. The objective of this study was to test, using image-based computational fluid dynamics (CFD), whether this is indeed the case. The lumen geometry was reconstructed from micro-CT scanning of a control Ldlr −/− mouse, and CFD simulations were carried out for both AR and control flow conditions derived from Doppler ultrasound measurements and literature data. Maps of time-averaged wall shear stress magnitude (TAWSS), oscillatory shear index (OSI) and relative residence time (RRT) were compared against the spatial distributions of plaque stained with oil red O, previously acquired in a group of AR and control mice. Maps of OSI and RRT were found to be consistent with plaque distributions in the AR mice and the absence of plaque in the control mice. TAWSS was uniformly lower under control vs. AR flow conditions, suggesting that levels (>100 dyn/cm2) exceeded those required to alone induce a pro-atherogenic response. Simulations of a straightened CFD model confirmed the importance of anatomical curvature for explaining the spatial distribution of lesions in the AR mice. In summary, oscillatory and retrograde flow induced in the AR mice, without concomitant low shear, may exacerbate or accelerate lesion formation, but the distinct anatomical curvature of the mouse aorta is responsible for the spatial distribution of lesions.

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Acknowledgments

The authors thank Lisa Yu for the micro-CT scanning. This work is part of the Mouse Imaging Centre at the Hospital for Sick Children and the University of Toronto. The infrastructure was funded by the Canada Foundation for Innovation and Ontario Innovation Trust. The research was funded by a CIHR Grant (102590), and the Heart and Stroke Foundation of Ontario (Grants T6107 and T6060). R.M.H. holds a Canada Research Chair. Y.H. and D.A.S. acknowledge the support of a Heart & Stroke Foundation Research Fellowship Award and Career Investigator Award, respectively.

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Authors and Affiliations

  1. Biomedical Simulation Laboratory, Department of Mechanical & Industrial Engineering, University of Toronto, Toronto, ON, Canada

    Yiemeng Hoi & David A. Steinman

  2. Mouse Imaging Centre, The Hospital for Sick Children, Toronto, ON, Canada

    Yu-Qing Zhou, Xiaoli Zhang & R. Mark Henkelman

  3. Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada

    Xiaoli Zhang & R. Mark Henkelman

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  1. Yiemeng Hoi
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  2. Yu-Qing Zhou
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  3. Xiaoli Zhang
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  5. David A. Steinman
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Correspondence to David A. Steinman.

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Associate Editor Joan Greve oversaw the review of this article.

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Hoi, Y., Zhou, YQ., Zhang, X. et al. Correlation Between Local Hemodynamics and Lesion Distribution in a Novel Aortic Regurgitation Murine Model of Atherosclerosis. Ann Biomed Eng 39, 1414–1422 (2011). https://doi.org/10.1007/s10439-011-0255-z

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  • DOI: https://doi.org/10.1007/s10439-011-0255-z

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