Cellular and Extracellular Matrix Basis for Heterogeneity in Mitral Annular Contraction

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dc.citation.firstpage151en_US
dc.citation.issueNumber2en_US
dc.citation.journalTitleCardiovascular Engineering and Technologyen_US
dc.citation.lastpage159en_US
dc.citation.volumeNumber6en_US
dc.contributor.authorStephens, Elizabeth H.en_US
dc.contributor.authorFahrenholtz, Monica M.en_US
dc.contributor.authorConnell, Patrick S.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. Jr.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.abstractRegional heterogeneity in mitral annular contraction, which is generally ascribed to the fibrous vs. muscular annular composition, ensures proper leaflet motion and timing of coaptation. It is unknown whether the fibroblast-like cells in the annulus modulate this heterogeneity, even though valvular interstitial cells (VICs) can be mechanically “activated.” Fourteen sheep underwent implantation of radiopaque markers around the mitral annulus defining four segments: septal (SEPT), lateral (LAT), and anterior (ANT-C) and posterior (POST-C) commissures. Segmental annular contraction was calculated using biplane videofluoroscopy. Immunohistochemistry of annular cross sections assessed regional matrix content, matrix turnover, and cell phenotype. Micropipette aspiration measured the effective modulus of the leaflets adjacent to the myocardial border. Whereas SEPT contained more collagen I and III, LAT demonstrated more collagen and elastin turnover as shown by greater decorin, lysyl oxidase, and matrix metalloprotease (MMP)-13 and smooth muscle alpha-actin (SMaA). This greater matrix turnover paralleled greater annular contraction in LAT vs. SEPT (22.5 vs. 4.1%). Similarly, POST-C had more SMaA and MMP13 than ANT-C, consistent with greater annular contraction in POST-C (18.8 vs. 11.1%). Interestingly, POST-C had the greatest effective modulus, significantly higher than LAT. These data suggest that matrix turnover by activated VICs relates to annular motion heterogeneity, maintains steady-state mechanical properties in the annulus, and could be a therapeutic target when annular motion is impaired. Conversely, alterations in this heterogeneous annular contraction, whether through disease or secondary to ring annuloplasty, could disrupt this normal pattern of cell-mediated matrix remodeling and further adversely impact mitral valve function.en_US
dc.identifier.citationStephens, Elizabeth H., Fahrenholtz, Monica M., Connell, Patrick S., et al.. "Cellular and Extracellular Matrix Basis for Heterogeneity in Mitral Annular Contraction." <i>Cardiovascular Engineering and Technology,</i> 6, no. 2 (2015) Springer: 151-159. http://dx.doi.org/10.1007/s13239-014-0209-3.en_US
dc.identifier.doihttp://dx.doi.org/10.1007/s13239-014-0209-3en_US
dc.identifier.urihttps://hdl.handle.net/1911/91369en_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.keywordannular contractionen_US
dc.subject.keywordcollagenen_US
dc.subject.keywordextracellular matrixen_US
dc.subject.keywordmatrix metalloproteasesen_US
dc.subject.keywordmitral annulusen_US
dc.titleCellular and Extracellular Matrix Basis for Heterogeneity in Mitral Annular Contractionen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpost-printen_US
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