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

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dc.citation.firstpage954en_US
dc.citation.issueNumber4en_US
dc.citation.journalTitleAnnals of Biomedical Engineeringen_US
dc.citation.lastpage967en_US
dc.citation.volumeNumber44en_US
dc.contributor.authorConnell, Patrick S.en_US
dc.contributor.authorAzimuddin, Anam F.en_US
dc.contributor.authorKim, Seulgi E.en_US
dc.contributor.authorRamirez, Fernandoen_US
dc.contributor.authorJackson, Matthew S.en_US
dc.contributor.authorLittle, Stephen H.en_US
dc.contributor.authorGrande-Allen, K. Janeen_US
dc.contributor.orgBioengineeringen_US
dc.date.accessioned2017-05-03T18:24:05Zen_US
dc.date.available2017-05-03T18:24:05Zen_US
dc.date.issued2016en_US
dc.description.abstractMitral 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.en_US
dc.identifier.citationConnell, Patrick S., Azimuddin, Anam F., Kim, Seulgi E., et al.. "Regurgitation Hemodynamics Alone Cause Mitral Valve Remodeling Characteristic of Clinical Disease States In Vitro." <i>Annals of Biomedical Engineering,</i> 44, no. 4 (2016) Springer: 954-967. https://doi.org/10.1007/s10439-015-1398-0.en_US
dc.identifier.doihttps://doi.org/10.1007/s10439-015-1398-0en_US
dc.identifier.urihttps://hdl.handle.net/1911/94138en_US
dc.language.isoengen_US
dc.publisherSpringeren_US
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Springer.en_US
dc.subject.keywordMitral valve regurgitationen_US
dc.subject.keywordMitral valve prolapseen_US
dc.subject.keywordFunctional mitral regurgitationen_US
dc.subject.keywordOrgan cultureen_US
dc.subject.keywordMyxomatous remodelingen_US
dc.titleRegurgitation Hemodynamics Alone Cause Mitral Valve Remodeling Characteristic of Clinical Disease States In Vitroen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpost-printen_US
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