| Regulation of valvular interstitial cell phenotype and function by hyaluronic acid in 2-D and 3-D culture environments. | |
| | |
MedLine Citation:
|
PMID: 20884350 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Disruption of the extracellular matrix (ECM) is frequently found in calcific aortic valve disease (CAVD), yet the role of ECM components in valvular interstitial cell (VIC) function and dysfunction remains poorly understood. This study examines the contributions of exogenous and endogenous hyaluronic acid (HA), in both two-dimensional (2-D) and 3-D environments, in regulating the phenotype and calcification of VICs. VIC calcification was first assessed in a 2-D setting in which the cells were exposed to different molecular weights of exogenous HA presented in either an immobilized or soluble form. Delivery of HA suppressed nodule formation in a molecular weight-dependent manner, while blocking VIC recognition of HA via an antibody to CD44 abolished these nodule-suppressive effects and stimulated other hallmarks of valvular dysfunction. These 2-D results were then validated in a more physiologically-relevant setting, using an approach that allowed the characterization of VIC phenotype in response to HA alterations in the native 3-D environment. In this approach, leaflet organ cultures were analyzed following treatment with anti-CD44 or with hyaluronidase to specifically remove HA. Disruption of VIC-HA interactions upregulated markers of VIC disease and induced leaflet mineralization. Similarly, HA-deficient leaflets exhibited numerous hallmarks of CAVD, including increased VIC proliferation, apoptosis, increased expression of disease-related markers, and mineralization. These findings suggest that VIC-HA interactions are crucial in maintaining a healthy VIC phenotype. Identification ECM components that can regulate VIC phenotype and function has significant implications for understanding native valve disease, investigating possible treatments, and designing new biomaterials for valve tissue engineering. |
| | |
Authors:
|
Karien J Rodriguez; Laura M Piechura; Kristyn S Masters |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-09-25 |
Journal Detail:
|
Title: Matrix biology : journal of the International Society for Matrix Biology Volume: 30 ISSN: 1569-1802 ISO Abbreviation: Matrix Biol. Publication Date: 2011 Jan |
Date Detail:
|
Created Date: 2011-01-31 Completed Date: 2011-07-01 Revised Date: 2012-02-01 |
Medline Journal Info:
|
Nlm Unique ID: 9432592 Medline TA: Matrix Biol Country: Netherlands |
Other Details:
|
Languages: eng Pagination: 70-82 Citation Subset: IM |
Copyright Information:
|
Copyright © 2010 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved. |
Affiliation:
|
Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Antigens, CD44 / metabolism Aortic Valve / pathology* Calcinosis Cell Culture Techniques Cells, Cultured Extracellular Matrix / metabolism Hyaluronic Acid / metabolism* Phenotype Swine |
| Grant Support | |
ID/Acronym/Agency:
|
R01 HL093281/HL/NHLBI NIH HHS; R01 HL093281-02/HL/NHLBI NIH HHS; R01 HL093281-04/HL/NHLBI NIH HHS; T32 HL 007936-06/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Antigens, CD44; 9004-61-9/Hyaluronic Acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Increased potential of a cationic liposome-based delivery system: enhancing stability and sustained ...
Next Document: Bacterial production of recombinant human poly(ADP-ribose) glycohydrolase.