Heterogeneity of Mitral Leaflet Matrix Composition and Turnover Correlates with Regional Leaflet Strain

dc.citation.firstpage141en_US
dc.citation.issueNumber2en_US
dc.citation.journalTitleCardiovascular Engineering and Technologyen_US
dc.citation.lastpage150en_US
dc.citation.volumeNumber6en_US
dc.contributor.authorStephens, Elizabeth H.en_US
dc.contributor.authorConnell, Patrick S.en_US
dc.contributor.authorFahrenholtz, Monica M.en_US
dc.contributor.authorTimek, Tomasz A.en_US
dc.contributor.authorDaughters, George T.en_US
dc.contributor.authorKuo, Joyce J.en_US
dc.contributor.authorPatton, Aaron M.en_US
dc.contributor.authorIngels, Neil B.en_US
dc.contributor.authorMiller, D. Craigen_US
dc.contributor.authorGrande-Allen, K. Janeen_US
dc.contributor.orgBioengineeringen_US
dc.date.accessioned2016-08-30T20:50:15Zen_US
dc.date.available2016-08-30T20:50:15Zen_US
dc.date.issued2015en_US
dc.description.abstractTo determine how extracellular matrix and contractile valvular cells contribute to the heterogeneous motion and strain across the mitral valve (MV) during the cardiac cycle, regional MV material properties, matrix composition, matrix turnover, and cell phenotype were related to regional leaflet strain. Radiopaque markers were implanted into 14 sheep to delineate the septal (SEPT), lateral (LAT), and anterior and posterior commissural leaflets (ANT-C, POST-C). Videofluoroscopy imaging was used to calculate radial and circumferential strains. Mechanical properties were assessed using uniaxial tensile testing and micropipette aspiration. Matrix composition and cell phenotypes were immunohistochemically evaluated within each leaflet region [basal leaflet (BL), mid-leaflet (ML), and free edge]. SEPT-BL segments were stiffer and stronger than other valve tissues, while LAT segments demonstrated more extensibility and strain. Collagens I and III in SEPT were greater than in LAT, although LAT showed greater collagen turnover [matrix metalloprotease (MMP)-13, lysyl oxidase] and cell activation [smooth muscle alpha-actin (SMaA), and non-muscle myosin (NMM)]. MMP13, NMM, and SMaA were strongly correlated with each other, as well as with radial and circumferential strains in both SEPT and LAT. SMaA and MMP13 in POST-C ML was greater than ANT-C, corresponding to greater radial strains in POST-C. This work directly relates leaflet strain, material properties, and matrix turnover, and suggests a role for myofibroblasts in the heterogeneity of leaflet composition and strain. New approaches to MV repair techniques and ring design should preserve this normal coupling between leaflet composition and motion.en_US
dc.identifier.citationStephens, Elizabeth H., Connell, Patrick S., Fahrenholtz, Monica M., et al.. "Heterogeneity of Mitral Leaflet Matrix Composition and Turnover Correlates with Regional Leaflet Strain." <i>Cardiovascular Engineering and Technology,</i> 6, no. 2 (2015) Springer: 141-150. http://dx.doi.org/10.1007/s13239-015-0214-1.en_US
dc.identifier.doihttp://dx.doi.org/10.1007/s13239-015-0214-1en_US
dc.identifier.urihttps://hdl.handle.net/1911/91370en_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.titleHeterogeneity of Mitral Leaflet Matrix Composition and Turnover Correlates with Regional Leaflet Strainen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpost-printen_US
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