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    Regurgitation Hemodynamics Alone Cause Mitral Valve Remodeling Characteristic of Clinical Disease States In Vitro

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    Author
    Connell, Patrick S.; Azimuddin, Anam F.; Kim, Seulgi E.; Ramirez, Fernando; Jackson, Matthew S.; More... Little, Stephen H.; Grande-Allen, K. Jane Less...
    Date
    2016
    Abstract
    Mitral valve regurgitation is a challenging clinical condition that is frequent, highly varied, and poorly understood. While the causes of mitral regurgitation are multifactorial, how the hemodynamics of regurgitation impact valve tissue remodeling is an understudied phenomenon. We employed a pseudo-physiological flow loop capable of long-term organ culture to investigate the early progression of remodeling in living mitral valves placed in conditions resembling mitral valve prolapse (MVP) and functional mitral regurgitation (FMR). Valve geometry was altered to mimic the hemodynamics of controls (no changes from native geometry), MVP (5ᅠmm displacement of papillary muscles towards the annulus), and FMR (5ᅠmm apical, 5ᅠmm lateral papillary muscle displacement, 65% larger annular area). Flow measurements ensured moderate regurgitant fraction for regurgitation groups. After 1-week culture, valve tissues underwent mechanical and compositional analysis. MVP conditioned tissues were less stiff, weaker, and had elevated collagen III and glycosaminoglycans. FMR conditioned tissues were stiffer, more brittle, less extensible, and had more collagen synthesis, remodeling, and crosslinking related enzymes and proteoglycans, including decorin, matrix metalloproteinase-1, and lysyl oxidase. These models replicate clinical findings of MVP (myxomatous remodeling) and FMR (fibrotic remodeling), indicating that valve cells remodel extracellular matrix in response to altered mechanical homeostasis resulting from disease hemodynamics.
    Citation
    Connell, Patrick S., Azimuddin, Anam F., Kim, Seulgi E., et al.. "Regurgitation Hemodynamics Alone Cause Mitral Valve Remodeling Characteristic of Clinical Disease States In Vitro." Annals of Biomedical Engineering, 44, no. 4 (2016) Springer: 954-967. https://doi.org/10.1007/s10439-015-1398-0.
    Published Version
    https://doi.org/10.1007/s10439-015-1398-0
    Keyword
    Mitral valve regurgitation; Mitral valve prolapse; Functional mitral regurgitation; Organ culture; Myxomatous remodeling
    Type
    Journal article
    Publisher
    Springer
    Citable link to this page
    https://hdl.handle.net/1911/94138
    Rights
    This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Springer.
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    • Bioengineering Publications [632]
    • Faculty Publications [4988]

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    Home | FAQ | Contact Us | Privacy Notice | Accessibility Statement
    Managed by the Digital Scholarship Services at Fondren Library, Rice University
    Physical Address: 6100 Main Street, Houston, Texas 77005
    Mailing Address: MS-44, P.O.BOX 1892, Houston, Texas 77251-1892
    Site Map