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Pregnancy-Induced Remodeling of Collagen Architecture and Content in the Mitral Valve

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Abstract

Pregnancy produces rapid, non-pathological volume-overload in the maternal circulation due to the demands of the growing fetus. Using a bovine model for human pregnancy, previous work in our laboratory has shown remarkable pregnancy-induced changes in leaflet size and mechanics of the mitral valve. The present study sought to relate these changes to structural alterations in the collagenous leaflet matrix. Anterior mitral valve leaflets were harvested from non-pregnant heifers and pregnant cows (pregnancy stage estimated by fetal length). We measured changes in the thickness of the leaflet and its anatomic layers via Verhoeff-Van Gieson staining, and in collagen crimp (wavelength and percent collagen crimped) via picrosirius red staining and polarized microscopy. Collagen concentration was determined biochemically: hydroxyproline assay for total collagen and pepsin-acid extraction for uncrosslinked collagen. Small-angle light scattering (SALS) assessed changes in internal fiber architecture (characterized by degree of fiber alignment and preferred fiber direction). Pregnancy produced significant changes to collagen structure in the mitral valve. Fiber alignment decreased 17% with an 11.5° rotation of fiber orientation toward the radial axis. Collagen fiber crimp was dramatically lost, accompanied by a 53% thickening of the fibrosa, and a 16% increase in total collagen concentration, both suggesting that new collagen is being synthesized. Extractable collagen concentration was low, both in the non-pregnant and pregnant state, suggesting early crosslinking of newly-synthesized collagen. This study has shown that the mitral valve is strongly adaptive during pregnancy, with significant changes in size, collagen content and architecture in response to rapidly changing demands.

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Acknowledgments

The authors thank Lucas Tedesco (Department of Bioengineering, University of Pittsburgh) for performing SALS data acquisition, Patricia Colp (Department of Pathology, Dalhousie University) for sharing expertise in histological staining techniques, Maxine Langman (Department of Applied Oral Sciences, Dalhousie University) for providing biochemical technical expertise, as well as O.H. Armstrong for the supply of bovine tissues.

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Authors and Affiliations

  1. School of Biomedical Engineering, Dalhousie University, 5981 University Avenue, Halifax, NS, B3H 3J5, Canada

    Caitlin M. Pierlot, J. Michael Lee & Sarah M. Wells

  2. Department of Applied Oral Sciences, Dalhousie University, Halifax, NS, Canada

    J. Michael Lee

  3. Department of Biomedical Engineering, The University of Akron, Akron, OH, USA

    Rouzbeh Amini

  4. Center for Cardiovascular Simulation, Institute for Computational Science and Engineering and the Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA

    Michael S. Sacks

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  1. Caitlin M. Pierlot
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  2. J. Michael Lee
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  5. Sarah M. Wells
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Correspondence to Sarah M. Wells.

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Associate Editor Jane Grande-Allen oversaw the review of this article.

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Pierlot, C.M., Lee, J.M., Amini, R. et al. Pregnancy-Induced Remodeling of Collagen Architecture and Content in the Mitral Valve. Ann Biomed Eng 42, 2058–2071 (2014). https://doi.org/10.1007/s10439-014-1077-6

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