Immune Mechanisms of Extracellular Matrix Remodeling in the Common Carotid: A Model of Intimal Hyperplasia

Persistent Link:
http://hdl.handle.net/10150/228464
Title:
Immune Mechanisms of Extracellular Matrix Remodeling in the Common Carotid: A Model of Intimal Hyperplasia
Author:
Robb, Tiffany Marie
Issue Date:
2012
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Intimal hyperplasia (IH) is characteristic of a cell population increase within the innermost layer of the arterial wall. It is hypothesized that extracellular matrix vascular remodeling secondary vascular injury is dependent upon the Th17 subset of the CD4+ lymphocytes. Male C57BL/6J and FVB/NJ murine strains underwent complete left common carotid artery ligation for periods of 14 and 28 days. A therapeutic simvastatin model was carried out in the FVB/NJ strain and involved a daily subcutaneous injection regimen of 40 mg/kg/mouse beginning 72 hours prior to and daily following a 14 day carotid ligation period. Histological and RT-PCR analysis was carried out with harvested carotid artery samples. The FVB/NJ 14 day and 28 day histological stains of the left common carotid artery following ligation injury developed evident structured and disassembled intimal hyperplasia, respectively. A gene array demonstrated dramatic expression of immune and cytokine transcription markers particularly in the FVB/NJ strain at both ligation time points. IL-17 and IL-6 transcriptional gene expression was upregulated greater than 20-fold in the FVB/NJ 28 day injury model. IL-17 transcription was significantly expressed by a change of 50.06 ± 0.19 (p = 0.004) in this strain at 28 days versus the control. Lastly, the simvastatin treatment model was found to exacerbate the immune response to ligation injury. These results revealed that the immune system elicits a role in the vascular remodeling that potentiates intimal hyperplasia.
Type:
text; Electronic Thesis
Keywords:
Vascular endothleial cell; Vascular smooth muscle cell; Pharmacology & Toxicology; Intimal hyperplasia; Simvastatin
Degree Name:
M.S.
Degree Level:
masters
Degree Program:
Graduate College; Pharmacology & Toxicology
Degree Grantor:
University of Arizona
Advisor:
Larson, Douglas F.

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleImmune Mechanisms of Extracellular Matrix Remodeling in the Common Carotid: A Model of Intimal Hyperplasiaen_US
dc.creatorRobb, Tiffany Marieen_US
dc.contributor.authorRobb, Tiffany Marieen_US
dc.date.issued2012-
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractIntimal hyperplasia (IH) is characteristic of a cell population increase within the innermost layer of the arterial wall. It is hypothesized that extracellular matrix vascular remodeling secondary vascular injury is dependent upon the Th17 subset of the CD4+ lymphocytes. Male C57BL/6J and FVB/NJ murine strains underwent complete left common carotid artery ligation for periods of 14 and 28 days. A therapeutic simvastatin model was carried out in the FVB/NJ strain and involved a daily subcutaneous injection regimen of 40 mg/kg/mouse beginning 72 hours prior to and daily following a 14 day carotid ligation period. Histological and RT-PCR analysis was carried out with harvested carotid artery samples. The FVB/NJ 14 day and 28 day histological stains of the left common carotid artery following ligation injury developed evident structured and disassembled intimal hyperplasia, respectively. A gene array demonstrated dramatic expression of immune and cytokine transcription markers particularly in the FVB/NJ strain at both ligation time points. IL-17 and IL-6 transcriptional gene expression was upregulated greater than 20-fold in the FVB/NJ 28 day injury model. IL-17 transcription was significantly expressed by a change of 50.06 ± 0.19 (p = 0.004) in this strain at 28 days versus the control. Lastly, the simvastatin treatment model was found to exacerbate the immune response to ligation injury. These results revealed that the immune system elicits a role in the vascular remodeling that potentiates intimal hyperplasia.en_US
dc.typetexten_US
dc.typeElectronic Thesisen_US
dc.subjectVascular endothleial cellen_US
dc.subjectVascular smooth muscle cellen_US
dc.subjectPharmacology & Toxicologyen_US
dc.subjectIntimal hyperplasiaen_US
dc.subjectSimvastatinen_US
thesis.degree.nameM.S.en_US
thesis.degree.levelmastersen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplinePharmacology & Toxicologyen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorLarson, Douglas F.en_US
dc.contributor.committeememberFrench, Edward D.en_US
dc.contributor.committeememberDavid, Thomas P.en_US
dc.contributor.committeememberDussor, Gregory O.en_US
All Items in UA Campus Repository are protected by copyright, with all rights reserved, unless otherwise indicated.