Document Detail

Hyaluronan turnover and hypoxic brown adipocytic differentiation are co-localized with ossification in calcified human aortic valves.
MedLine Citation:
PMID:  23017666     Owner:  NLM     Status:  MEDLINE    
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.
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
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-09-25
Journal Detail:
Title:  Pathology, research and practice     Volume:  208     ISSN:  1618-0631     ISO Abbreviation:  Pathol. Res. Pract.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-12     Completed Date:  2013-05-28     Revised Date:  2013-12-04    
Medline Journal Info:
Nlm Unique ID:  7806109     Medline TA:  Pathol Res Pract     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  642-50     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier GmbH. All rights reserved.
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MeSH Terms
Adipocytes, Brown / metabolism,  pathology*
Anoxia / metabolism*
Aortic Valve / metabolism*,  pathology,  surgery
Aortic Valve Stenosis / metabolism*,  pathology
Biological Markers / metabolism
Calcinosis / etiology,  metabolism*,  pathology
Cell Adhesion Molecules / metabolism
Cell Differentiation
Glucuronosyltransferase / metabolism
Homeostasis / physiology
Hyaluronic Acid / metabolism*
Hyaluronoglucosaminidase / metabolism
Ossification, Heterotopic / metabolism,  pathology*
Grant Support
Reg. No./Substance:
0/Biological Markers; 0/Cell Adhesion Molecules; 0/TNFAIP6 protein, human; 9004-61-9/Hyaluronic Acid; EC; EC synthase; EC

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