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Multifunctional polymers for inhibition of oxidized lipoprotein accumulation and inflammation in macrophage cells

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TypeOfResource
Text
TitleInfo (ID = T-1)
Title
Multifunctional polymers for inhibition of oxidized lipoprotein accumulation and inflammation in macrophage cells
Identifier
ETD_2492
Identifier (type = hdl)
http://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.000053095
Language
LanguageTerm (authority = ISO639-2); (type = code)
eng
Genre (authority = marcgt)
theses
Subject (ID = SBJ-1); (authority = RUETD)
Topic
Biomedical Engineering
Subject (ID = SBJ-2); (authority = ETD-LCSH)
Topic
Macrophages
Subject (ID = SBJ-3); (authority = ETD-LCSH)
Topic
Low density lipoproteins
Subject (ID = SBJ-4); (authority = ETD-LCSH)
Topic
Atherosclerosis--Treatment
Subject (ID = SBJ-5); (authority = ETD-LCSH)
Topic
Polymers in medicine
Abstract (type = abstract)
A major cause of cardiovascular disease is atherosclerosis, the progressive accumulation and modification of low density lipoproteins (LDL) within the vascular wall associated with a non-reversible inflammatory cascade. Current treatments attempt to inhibit systemic LDL levels, and thus can only secondarily de-escalate the progression of atherosclerosis. This thesis investigates the mechanisms of an alternative approach based on the use of amphiphilic polymers to directly inhibit highly oxidized LDL (hoxLDL) internalization by macrophage cells, thereby retarding foam cell formation and inflammatory cytokine secretion. First the architecture of the polymers is systematically investigated to elucidate the important design facets for hoxLDL uptake inhibition by THP-1 human macrophage cells in serum and serum free media. The optimal polymer structure is found to be comprised of one, rotationally restricted carboxylic acid conjugated to the hydrophobic end of each polymer chain. Through the administration of carboxy-terminated amphiphilic polymers (AMs) the total concentration of hoxLDL within macrophage cells is lowered by 73% and when an encapsulated Liver-X Receptor (LXR) ligand is also delivered the hoxLDL accumulation is further lowered, decreased by 88%. The delivery of the AMs and drug encapsulated AMs in vivo shows a significant inhibition in cholesterol accumulation and macrophage recruitment in an injured carotid artery rat model. The AMs also inhibit inflammatory responses in vitro, significantly decreasing matrix metalloproteinase (57%) and cytokine secretion (TNFα 47% and IL-1β 59%) compared to non-treated cells. Through the inhibition of hoxLDL internalization and inflammation progression these AMs show the potential to be a new and multi-faceted cardiovascular treatment modality.
PhysicalDescription
Form (authority = gmd)
electronic resource
Extent
xii, 177 p. : ill.
InternetMediaType
application/pdf
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text/xml
Note (type = degree)
Ph.D.
Note
Includes abstract
Note
Vita
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Nicole M Iverson
Name (ID = NAME-1); (type = personal)
NamePart (type = family)
Iverson
NamePart (type = given)
Nicole M
NamePart (type = date)
1981-
Role
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author
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Nicole Iverson
Name (ID = NAME-2); (type = personal)
NamePart (type = family)
Moghe
NamePart (type = given)
Prabhas V
Role
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chair
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Advisory Committee
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Prabhas V Moghe
Name (ID = NAME-3); (type = personal)
NamePart (type = family)
Uhrich
NamePart (type = given)
Kathryn E
Role
RoleTerm (authority = RULIB)
internal member
Affiliation
Advisory Committee
DisplayForm
Kathryn E Uhrich
Name (ID = NAME-4); (type = personal)
NamePart (type = family)
Nackman
NamePart (type = given)
Gary B
Role
RoleTerm (authority = RULIB)
internal member
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Advisory Committee
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Gary B Nackman
Name (ID = NAME-5); (type = personal)
NamePart (type = family)
Roth
NamePart (type = given)
Charles M
Role
RoleTerm (authority = RULIB)
internal member
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Advisory Committee
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Charles M Roth
Name (ID = NAME-6); (type = personal)
NamePart (type = family)
Dixon
NamePart (type = given)
Joseph L
Role
RoleTerm (authority = RULIB)
outside member
Affiliation
Advisory Committee
DisplayForm
Joseph L Dixon
Name (ID = NAME-1); (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (ID = NAME-2); (type = corporate)
NamePart
Graduate School - New Brunswick
Role
RoleTerm (authority = RULIB)
school
OriginInfo
DateCreated (qualifier = exact)
2010
DateOther (qualifier = exact); (type = degree)
2010
Place
PlaceTerm (type = code)
xx
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
RelatedItem (type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier (type = local)
rucore19991600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier (type = doi)
doi:10.7282/T3FN1684
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Rights

RightsDeclaration (AUTHORITY = GS); (ID = rulibRdec0006)
The author owns the copyright to this work.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
RightsHolder (ID = PRH-1); (type = personal)
Name
FamilyName
Iverson
GivenName
Nicole
Role
Copyright Holder
RightsEvent (ID = RE-1); (AUTHORITY = rulib)
Type
Permission or license
DateTime
2010-03-12 17:11:03
AssociatedEntity (ID = AE-1); (AUTHORITY = rulib)
Role
Copyright holder
Name
Nicole Iverson
Affiliation
Rutgers University. Graduate School - New Brunswick
AssociatedObject (ID = AO-1); (AUTHORITY = rulib)
Type
License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
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Technical

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ETD
MimeType (TYPE = file)
application/pdf
MimeType (TYPE = container)
application/x-tar
FileSize (UNIT = bytes)
3450880
Checksum (METHOD = SHA1)
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