Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-1-26
pubmed:abstractText
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 TGF?1 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 TGF?1). 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 TGF?1 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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1932-7005
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 John Wiley & Sons, Ltd.
pubmed:issnType
Electronic
pubmed:volume
5
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
85-96
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Impact of pre-existing elastic matrix on TGF?1 and HA oligomer-induced regenerative elastin repair by rat aortic smooth muscle cells.
pubmed:affiliation
Department of Bioengineering, Clemson University, 173 Ashley Avenue, Clemson, SC 29425, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural