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  • Review Article
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Role of biomechanical forces in the natural history of coronary atherosclerosis

Nature Reviews Cardiology volume 13, pages 210–220 (2016)Cite this article

Subjects

Key Points

  • Atherosclerotic plaques are not uniformly distributed throughout the coronary tree, indicating that local mechanical factors might determine plaque development and growth

  • Blood flow and particularly wall shear stress heavily influence endothelial function through diverse mechanisms

  • Biomechanical forces promote adverse changes in plaque composition, promoting a high-risk plaque phenotype that is more prone to rupture, and can result in sudden cardiac events

  • Plaque structural stress is determined by plaque composition, with plaque rupture occurring when plaque structural stress exceeds plaque strength

  • Prospective, observational studies suggest that integrating biomechanical parameters can improve our ability to identify the patients at highest risk of rapid disease progression or plaque rupture

Abstract

Atherosclerosis remains a major cause of morbidity and mortality worldwide, and a thorough understanding of the underlying pathophysiological mechanisms is crucial for the development of new therapeutic strategies. Although atherosclerosis is a systemic inflammatory disease, coronary atherosclerotic plaques are not uniformly distributed in the vascular tree. Experimental and clinical data highlight that biomechanical forces, including wall shear stress (WSS) and plaque structural stress (PSS), have an important role in the natural history of coronary atherosclerosis. Endothelial cell function is heavily influenced by changes in WSS, and longitudinal animal and human studies have shown that coronary regions with low WSS undergo increased plaque growth compared with high WSS regions. Local alterations in WSS might also promote transformation of stable to unstable plaque subtypes. Plaque rupture is determined by the balance between PSS and material strength, with plaque composition having a profound effect on PSS. Prospective clinical studies are required to ascertain whether integrating mechanical parameters with medical imaging can improve our ability to identify patients at highest risk of rapid disease progression or sudden cardiac events.

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Figure 1: Biomechanical forces in atherosclerosis.
Figure 2: Wall shear stress calculations.
Figure 3: Plaque structural stress calculations.
Figure 4: Proinflammatory pathways regulated by mechanical sensing.

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Acknowledgements

The authors were supported by the British Heart Foundation (FS/13/33/30168), Heart Research UK (RG2638/14/16), the Cambridge NIHR Biomedical Research Centre, and the BHF Cambridge Centre for Research Excellence. The authors would also like to thank Shuo Wang (Department of Radiology, University of Cambridge, UK) for the preparation of the images for publication.

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Authors and Affiliations

  1. Division of Cardiovascular Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK

    Adam J. Brown & Martin R. Bennett

  2. Department of Radiology, University of Cambridge, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK

    Zhongzhao Teng & Jonathan H. Gillard

  3. Department of Cardiovascular Science, University of Sheffield, Western Bank, Sheffield, S10 2TN, UK

    Paul C. Evans

  4. Department of Medicine, Emory University, 100 Woodruff Circle, Atlanta, 30322, Georgia, USA

    Habib Samady

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A.J.B., Z.T., and P.C. researched data for the article, and wrote and edited the manuscript. J.H.G., H.S., and M.R.B. discussed the content, and reviewed and edited the manuscript before submission.

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Brown, A., Teng, Z., Evans, P. et al. Role of biomechanical forces in the natural history of coronary atherosclerosis. Nat Rev Cardiol 13, 210–220 (2016). https://doi.org/10.1038/nrcardio.2015.203

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