Retrovirally induced dilated cardiomyopathy in murine acquired immunodeficiency syndrome

Persistent Link:
http://hdl.handle.net/10150/280256
Title:
Retrovirally induced dilated cardiomyopathy in murine acquired immunodeficiency syndrome
Author:
Beischel, Julie M.
Issue Date:
2003
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:
Acquired immunodeficiency syndrome (AIDS) has been associated with several cardiovascular abnormalities including dilated cardiomyopathy (DCM). DCM is characterized by dilation of the left ventricle and abnormal systolic and diastolic left ventricular function and is often associated with myocarditis and alterations in the extracellular matrix. The prevalence and severity of AIDS-associated DCM necessitates a better understanding of its disease process. To study AIDS DCM, the LP-BM5 murine AIDS (MAIDS) model, which offers many similarities to AIDS and several advantages as a model, was used. The cardiac function of MAIDS mice was compared to control mice using a conductance catheter system and left ventricular dimensions and compliance were significantly altered indicating a dilated cardiomyopathy. Competitive polymerase chain reaction was used to quantify the LP-BM5 retrovirus in splenic and cardiac tissue from MAIDS mice and illustrated active viral replication in spleen as well as heart tissue during the disease process. Immunohistochemistry and Northern blot analysis were used to determine the role of inflammation in this process: No staining was observed for immune cell infiltrates or the inflammatory mediators tumor necrosis factor-alpha and inducible nitric oxide synthase. The content of cardiac collagen, the major determinant of ventricular architecture, was significantly decreased in MAIDS mice compared to controls and LP-BM5 was shown to infect cardiac fibroblasts in vitro. Pharmacological treatment with zidovudine and/or indinavir prevented cardiac dysfunction through decreases in viral load without functional cardiotoxicity.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Health Sciences, Pharmacology.; Health Sciences, Pathology.; Health Sciences, Immunology.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Pharmacology and Toxicology
Degree Grantor:
University of Arizona
Advisor:
Larson, Douglas F.

Full metadata record

DC FieldValue Language
dc.language.isoen_USen_US
dc.titleRetrovirally induced dilated cardiomyopathy in murine acquired immunodeficiency syndromeen_US
dc.creatorBeischel, Julie M.en_US
dc.contributor.authorBeischel, Julie M.en_US
dc.date.issued2003en_US
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.abstractAcquired immunodeficiency syndrome (AIDS) has been associated with several cardiovascular abnormalities including dilated cardiomyopathy (DCM). DCM is characterized by dilation of the left ventricle and abnormal systolic and diastolic left ventricular function and is often associated with myocarditis and alterations in the extracellular matrix. The prevalence and severity of AIDS-associated DCM necessitates a better understanding of its disease process. To study AIDS DCM, the LP-BM5 murine AIDS (MAIDS) model, which offers many similarities to AIDS and several advantages as a model, was used. The cardiac function of MAIDS mice was compared to control mice using a conductance catheter system and left ventricular dimensions and compliance were significantly altered indicating a dilated cardiomyopathy. Competitive polymerase chain reaction was used to quantify the LP-BM5 retrovirus in splenic and cardiac tissue from MAIDS mice and illustrated active viral replication in spleen as well as heart tissue during the disease process. Immunohistochemistry and Northern blot analysis were used to determine the role of inflammation in this process: No staining was observed for immune cell infiltrates or the inflammatory mediators tumor necrosis factor-alpha and inducible nitric oxide synthase. The content of cardiac collagen, the major determinant of ventricular architecture, was significantly decreased in MAIDS mice compared to controls and LP-BM5 was shown to infect cardiac fibroblasts in vitro. Pharmacological treatment with zidovudine and/or indinavir prevented cardiac dysfunction through decreases in viral load without functional cardiotoxicity.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectHealth Sciences, Pharmacology.en_US
dc.subjectHealth Sciences, Pathology.en_US
dc.subjectHealth Sciences, Immunology.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplinePharmacology and Toxicologyen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorLarson, Douglas F.en_US
dc.identifier.proquest3089910en_US
dc.identifier.bibrecord.b44417779en_US
All Items in UA Campus Repository are protected by copyright, with all rights reserved, unless otherwise indicated.