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

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dc.citation.firstpage642en_US
dc.citation.issueNumber11en_US
dc.citation.journalTitlePathology - Research and Practiceen_US
dc.citation.lastpage650en_US
dc.citation.volumeNumber208en_US
dc.contributor.authorStephens, Elizabeth H.en_US
dc.contributor.authorSaltarrelli, Jerome G. Jr.en_US
dc.contributor.authorBalaoing, Liezl R.en_US
dc.contributor.authorBaggett, L. Scotten_US
dc.contributor.authorNandi, Indrajiten_US
dc.contributor.authorAnderson, Kristin M.en_US
dc.contributor.authorMorrisett, Joel D.en_US
dc.contributor.authorReardon, Michael J.en_US
dc.contributor.authorSimpson, Melanie A.en_US
dc.contributor.authorWeigel, Paul H.en_US
dc.contributor.authorOlmsted-Davis, Elizabeth A.en_US
dc.contributor.authorDavis, Alan R.en_US
dc.contributor.authorGrande-Allen, K. Janeen_US
dc.contributor.orgBioengineeringen_US
dc.contributor.orgStatisticsen_US
dc.date.accessioned2014-11-21T21:26:57Zen_US
dc.date.available2014-11-21T21:26:57Zen_US
dc.date.issued2012en_US
dc.description.abstractThe 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.en_US
dc.identifier.citationStephens, 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." <i>Pathology - Research and Practice,</i> 208, no. 11 (2012) Elsevier: 642-650. http://dx.doi.org/10.1016/j.prp.2012.08.001.en_US
dc.identifier.doihttp://dx.doi.org/10.1016/j.prp.2012.08.001en_US
dc.identifier.urihttps://hdl.handle.net/1911/78486en_US
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Elsevier.en_US
dc.subject.keywordbrown adipocytesen_US
dc.subject.keywordhyaluronanen_US
dc.subject.keywordhypoxiaen_US
dc.subject.keywordcalcificationen_US
dc.subject.keywordaortic valveen_US
dc.titleHyaluronan turnover and hypoxic brown adipocytic differentiation are co-localized with ossification in calcified human aortic valvesen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpost-printen_US
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