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    Hyaluronan turnover and hypoxic brown adipocytic differentiation are co-localized with ossification in calcified human aortic valves

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    Stephens, Elizabeth H.; Saltarrelli, Jerome G. Jr.; Balaoing, Liezl R.; Baggett, L. Scott; Nandi, Indrajit; More... Anderson, Kristin M.; Morrisett, Joel D.; Reardon, Michael J.; Simpson, Melanie A.; Weigel, Paul H.; Olmsted-Davis, Elizabeth A.; Davis, Alan R.; Grande-Allen, K. Jane Less...
    Date
    2012
    Abstract
    The calcification process in aortic stenosis has garnered considerable interest but only limited investigation into selected signaling pathways. This study investigated mechanisms related to hypoxia, hyaluronan homeostasis, brown adipocytic differentiation, and ossification within calcified valves. Surgically explanted calcified aortic valves (nᅠ=ᅠ14) were immunostained for markers relevant to these mechanisms and evaluated in the center (NodCtr) and edge (NodEdge) of the calcified nodule (NodCtr), tissue directly surrounding nodule (NodSurr); center and tissue surrounding small モprenodulesヤ (PreNod, PreNodSurr); and normal fibrosa layer (CollFibr). Pearson correlations were determined between staining intensities of markers within regions. Ossification markers primarily localized to NodCtr and NodEdge, along with markers related to hyaluronan turnover and hypoxia. Markers of brown adipocytic differentiation were frequently co-localized with markers of hypoxia. In NodCtr and NodSurr, brown fat and ossification markers correlated with hyaluronidase-1, whereas these markers, as well as hypoxia, correlated with hyaluronan synthases in NodEdge. The protein product of tumor necrosis factor-? stimulated gene-6 strongly correlated with ossification markers and hyaluronidase in the regions surrounding the nodules (NodSurr, PreNodSurr). In conclusion, this study suggests roles for hyaluronan homeostasis and the promotion of hypoxia by cells demonstrating brown fat markers in calcific aortic valve disease.
    Citation
    Stephens, Elizabeth H., Saltarrelli, Jerome G. Jr., Balaoing, Liezl R., et al.. "Hyaluronan turnover and hypoxic brown adipocytic differentiation are co-localized with ossification in calcified human aortic valves." Pathology - Research and Practice, 208, no. 11 (2012) Elsevier: 642-650. http://dx.doi.org/10.1016/j.prp.2012.08.001.
    Published Version
    http://dx.doi.org/10.1016/j.prp.2012.08.001
    Keyword
    brown adipocytes; hyaluronan; hypoxia; calcification; aortic valve
    Type
    Journal article
    Publisher
    Elsevier
    Citable link to this page
    https://hdl.handle.net/1911/78486
    Rights
    This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Elsevier.
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    • Bioengineering Publications [626]
    • Faculty Publications [4918]
    • Statistics Publications [136]

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    Home | FAQ | Contact Us | Privacy Notice | Accessibility Statement
    Managed by the Digital Scholarship Services at Fondren Library, Rice University
    Physical Address: 6100 Main Street, Houston, Texas 77005
    Mailing Address: MS-44, P.O.BOX 1892, Houston, Texas 77251-1892
    Site Map