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Title of Journal: Cardiovasc Eng Tech

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Abbravation: Cardiovascular Engineering and Technology

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Springer US

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DOI

10.1007/bf01602304

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ISSN

1869-4098

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Cellular and Extracellular Matrix Basis for Hetero

Authors: Elizabeth H Stephens Monica M Fahrenholtz Patrick S Connell Tomasz A Timek George T Daughters Joyce J Kuo Aaron M Patton Neil B Ingels D Craig Miller K Jane GrandeAllen
Publish Date: 2015/01/08
Volume: 6, Issue: 2, Pages: 151-159
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Abstract

Regional 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 fibroblastlike 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 ANTC and posterior POSTC 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 MMP13 and smooth muscle alphaactin SMaA This greater matrix turnover paralleled greater annular contraction in LAT vs SEPT 225 vs 41 Similarly POSTC had more SMaA and MMP13 than ANTC consistent with greater annular contraction in POSTC 188 vs 111 Interestingly POSTC had the greatest effective modulus significantly higher than LAT These data suggest that matrix turnover by activated VICs relates to annular motion heterogeneity maintains steadystate 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 cellmediated matrix remodeling and further adversely impact mitral valve functionThe authors appreciate assistance from Indrajit Nandi the statistical expertise of Dr Scott Baggett and the micropipette aspiration equipment from Dr Robert Raphael Funding for this project came in part from graduate fellowships from the Hertz Foundation EHS National Institutes of Health F30HL094019 EHS and American Heart Association PSC and National Institutes of Health grants R01HL067025 and R01HL029589 DCMElizabeth H Stephens was supported by individual graduate fellowships from the Hertz Foundation and NIH F30HL094019 Patrick S Connell was supported by an individual fellowship from the American Heart Association D Craig Miller was supported by NIH R01 HL067025 and R01 HL029589 K Jane GrandeAllen has served as a consultant for Edwards Lifesciences Monica M Fahrenholtz declares that she has no conflict of interest Tomasz A Timek declares that he has no conflict of interest George T Daughters declares that he has no conflict of interest Joyce J Kuo declares that she has no conflict of interest Aaron M Patton declares that he has no conflict of interest Neil B Ingels Jr declares that he has no conflict of interest


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