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Heart Valve Mechanobiology in Development and Disease

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Molecular and Cellular Mechanobiology

Part of the book series: Physiology in Health and Disease ((PIHD))

Abstract

Heart valves reside in one of the most mechanically demanding environments within the body, experiencing over 100,000 cycles daily of a combination of biomechanical and hemodynamic forces. The forces applied to heart valves are critical for proper valvulogenesis and normal valve function and maintenance, but disruptions in the mechanical environment can lead to developmental defects and disease. In this chapter, we review current understanding of the roles of hemodynamic forces in valve development, from the initiation of valvulogenesis by cardiac jelly formation, to the invasion of cells into the cardiac cushion through the process of endothelial-to-mesenchymal transition (EndMT) and subsequent remodeling of the extracellular matrix to give rise to the tri-layered structure of developed valves. We also review growing evidence that implicates shear stress, cyclic strain, and matrix mechanics in regulating the initiation and progression of calcific aortic valve disease (CAVD), the most common adult valve disease for which there currently is no medical therapy. An improved understanding of how mechanical forces regulate valve development and disease is expected to help identify therapeutic targets for the treatment of adult valve diseases and to guide the design of living tissue replacement valves for patients with congenital valve defects or diseased valves.

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Authors and Affiliations

  1. Translational Biology and Engineering Program, Ted Rogers Centre for Heart Research, 661 University Avenue, 14th floor, Toronto, ON, Canada, M5G 1M1

    Aileen Zhong & Craig A. Simmons Ph.D.

  2. Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada

    Aileen Zhong & Craig A. Simmons Ph.D.

  3. Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, ON, Canada

    Craig A. Simmons Ph.D.

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  1. Aileen Zhong
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Correspondence to Craig A. Simmons Ph.D. .

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Editors and Affiliations

  1. Professor of Bioengineering and Medicine, University of California, San Diego, La Jolla, California, USA

    Shu Chien

  2. Associate Professor of Bioengineering, University of California, San Diego, La Jolla, California, USA

    Adam J. Engler

  3. Associate Professor of Bioengineering, University of California, San Diego, La Jolla, California, USA

    Peter Yingxiao Wang

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Zhong, A., Simmons, C.A. (2016). Heart Valve Mechanobiology in Development and Disease. In: Chien, S., Engler, A., Wang, P. (eds) Molecular and Cellular Mechanobiology. Physiology in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-5617-3_12

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