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

Elizabeth H. Stephens, Jerome G. Saltarrelli, Liezl R. Balaoing, L. Scott Baggett, Indrajit Nandi, Kristin M. Anderson, Joel D. Morrisett, Michael J. Reardon, Melanie A. Simpson, Paul H. Weigel, Elizabeth A. Olmsted-Davis, Alan R. Davis, K. Jane Grande-Allen

Research output: Contribution to journalArticle

9 Scopus citations

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 (n=14) 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 "prenodules" (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-α 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.

Original languageEnglish (US)
Pages (from-to)642-650
Number of pages9
JournalPathology Research and Practice
Volume208
Issue number11
DOIs
StatePublished - Nov 15 2012

Keywords

  • Aortic valve
  • Brown adipocytes
  • Calcification
  • Hyaluronan
  • Hypoxia

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Cell Biology

Fingerprint Dive into the research topics of 'Hyaluronan turnover and hypoxic brown adipocytic differentiation are co-localized with ossification in calcified human aortic valves'. Together they form a unique fingerprint.

  • Cite this

    Stephens, E. H., Saltarrelli, J. G., Balaoing, L. R., Baggett, L. S., Nandi, I., Anderson, K. M., Morrisett, J. D., Reardon, M. J., Simpson, M. A., Weigel, P. H., Olmsted-Davis, E. A., Davis, A. R., & Grande-Allen, K. J. (2012). Hyaluronan turnover and hypoxic brown adipocytic differentiation are co-localized with ossification in calcified human aortic valves. Pathology Research and Practice, 208(11), 642-650. https://doi.org/10.1016/j.prp.2012.08.001