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

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dc.citation.firstpage954
dc.citation.issueNumber4
dc.citation.journalTitleAnnals of Biomedical Engineering
dc.citation.lastpage967
dc.citation.volumeNumber44
dc.contributor.authorConnell, Patrick S.
dc.contributor.authorAzimuddin, Anam F.
dc.contributor.authorKim, Seulgi E.
dc.contributor.authorRamirez, Fernando
dc.contributor.authorJackson, Matthew S.
dc.contributor.authorLittle, Stephen H.
dc.contributor.authorGrande-Allen, K. Jane
dc.date.accessioned2017-05-03T18:24:05Z
dc.date.available2017-05-03T18:24:05Z
dc.date.issued2016
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.
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.
dc.identifier.doihttps://doi.org/10.1007/s10439-015-1398-0
dc.identifier.urihttps://hdl.handle.net/1911/94138
dc.language.isoeng
dc.publisherSpringer
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Springer.
dc.subject.keywordMitral valve regurgitation
dc.subject.keywordMitral valve prolapse
dc.subject.keywordFunctional mitral regurgitation
dc.subject.keywordOrgan culture
dc.subject.keywordMyxomatous remodeling
dc.titleRegurgitation Hemodynamics Alone Cause Mitral Valve Remodeling Characteristic of Clinical Disease States In Vitro
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpost-print
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