| Impact of pre-existing elastic matrix on TGFβ1 and HA oligomer-induced regenerative elastin repair by rat aortic smooth muscle cells. | |
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MedLine Citation:
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PMID: 20653044 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Regenerating elastic matrices lost to disease (e.g. in aneurysms) is vital to re-establishing vascular homeostasis but is challenged by the poor elastogenicity of post-neonatal cells. We previously showed that exogenous hyaluronan oligomers (HA-o) and TGFβ1 synergistically enhance tropo- and matrix elastin deposition by healthy adult rat aortic SMCs (RASMCs). Towards treating aortic aneurysms (AAs), which exhibit cause- and site-specific heterogeneity in matrix content/structure and contain proteolytically-injured SMCs, we investigated the impact of pre-existing elastic matrix degeneration on elastogenic induction of injured RASMCs. Elastin-rich RASMC layers at 21 days of culture were treated with 0.15 U/ml (PPE15) and 0.75 U/ml (PPE75) porcine pancreatic elastase to degrade the elastic matrix variably, or left uninjured (control). One set of cultures was harvested at 21 days, before and after injury, to quantify viable cell count, matrix elastin loss. Other injured cell layers were cultured to 42 days with or without factors (0.2 µg/ml HA oligomers, 1 ng/ml TGFβ1). We showed that: (a) the ability of cultures to self-repair and regenerate elastic matrices following proteolysis is limited when elastolysis is severe; (b) HA oligomers and TGFβ1 elastogenically stimulate RASMCs in mildly-injured (i.e. PPE15) cultures to restore both elastic matrix amounts and elastic fibre deposition to levels in healthy cultures; and (c) in severely injured (i.e. PPE75) cultures, the factors stimulate matrix elastin synthesis and crosslinking, although not to control levels. The outcomes underscore the need to enhance elastogenic factor doses based on the severity of elastin loss. This study will help in customizing therapies for elastin regeneration within AAs, based on cause and location. |
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Authors:
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Carmen E Gacchina; Anand Ramamurthi |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Journal of tissue engineering and regenerative medicine Volume: 5 ISSN: 1932-7005 ISO Abbreviation: J Tissue Eng Regen Med Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-26 Completed Date: 2011-04-25 Revised Date: 2013-03-11 |
Medline Journal Info:
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Nlm Unique ID: 101308490 Medline TA: J Tissue Eng Regen Med Country: England |
Other Details:
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Languages: eng Pagination: 85-96 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 John Wiley & Sons, Ltd. |
Affiliation:
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Department of Bioengineering, Clemson University, 173 Ashley Avenue, Clemson, SC 29425, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Aorta / cytology*, metabolism Aortic Aneurysm / metabolism, therapy Cells, Cultured Elasticity Elastin* Extracellular Matrix* Hyaluronic Acid* Myocytes, Smooth Muscle / cytology*, metabolism Pancreatic Elastase / pharmacology Rats Rats, Sprague-Dawley Regeneration* Swine Tissue Engineering / methods Transforming Growth Factor beta1 / pharmacology* |
| Grant Support | |
ID/Acronym/Agency:
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C06 RR018823-01/RR/NCRR NIH HHS; C06RR018823/RR/NCRR NIH HHS; EB006078-01A1/EB/NIBIB NIH HHS; HL007260/HL/NHLBI NIH HHS; P20 RR016461-04/RR/NCRR NIH HHS; P20RR016461/RR/NCRR NIH HHS; R01 HL092051-01A1/HL/NHLBI NIH HHS; R01 HL092051-04/HL/NHLBI NIH HHS; R01 HL092051-05/HL/NHLBI NIH HHS; R21 EB006078-01A1/EB/NIBIB NIH HHS; T32 HL007260/HL/NHLBI NIH HHS; T32 HL007260-33/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Transforming Growth Factor beta1; 9004-61-9/Hyaluronic Acid; 9007-58-3/Elastin; EC 3.4.21.36/Pancreatic Elastase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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