Mechanistic Consequences of Cardiac Oxidative Stress

Mechanistic Consequences of Cardiac Oxidative Stress

Bibliographic Details
Main Author: Han, Bing
Language:English
Published: The Ohio State University / OhioLINK 2008
Subjects:
Pharmacology
cardiovascular
diabetes
oxidative stress
glutathione
cocaine
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=osu1203478009
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-osu12034780092021-08-03T05:53:19Z Mechanistic Consequences of Cardiac Oxidative Stress Han, Bing Pharmacology cardiovascular diabetes oxidative stress glutathione cocaine <p>This thesis deals with understanding the mechanistic consequences of cardiac oxidative stress in non-ischemic cardiovascular complications settings including type I diabetes and cocaine related cardiovascular complications. It is intended to provide novel mechanistic insights into these complications so that specialized therapy can be developed to treat these complications. Additional components of this dissertation deals with the appropriate use of stress testing in mice in addition to basal cardiovascular function measurements.</p><p>Using a murine type 1 diabetes model we tested the hypothesis that alterations in cardiac performance were associated with myocardial oxidative stress. The data demonstrate that the mouse model of STZ induced type-1 diabetes mimics the cardiovascular abnormalities observed in clinical settings with respect to non-ischemic contractile alterations, electrophysiological abnormalities and microvascular rarefaction and that these changes are related to oxidative stress, perturbations in myocardial vascular endothelial growth factor (VEGF) isoforms and/or connexin regulation. These findings also implicate GSH depletion and/or GSSG accumulation as participants in this setting.</p><p>In subsequent investigations we observed that cardiac GSH depletion in normal mice causes increased cardiac oxidative stress and modulates cardiac performance. Using buthionine sulfoximine (BSO) cardiac GSH/GSSG was significant reduced at 24hr. Elongation of QTc and QRS, impaired diastolic performance, and increased cardiac output were observed. Moderate cardiovascular stress testing decreased cardiac contractile function and provoked an increase in arrhythmias in animals pretreated with BSO. These cardiac effects were associated with oxidative insults to key components of the contractile and electrical apparatus, such as, desmin, troponin (T), ERG and Cx43. </p><p>In addition, we investigated cocaine related acute and chronic cardiovascular dysfunction using a mouse model and explored the inter-relationship among oxidative stress, protracted cardiac abnormities and acute cardiac work load stress. Cardiovascular abnormalities were observed in murine model, similar to clinical phenomenon. Extensive dysregulation of reactive nitrogen species were observed as evidenced by increased cardiac prevalence of NOS2 and protein-3NT. These oxidant status changes were correlated to cardiac function changes, suggesting that cardiac dysfunction might be mediated by oxidative stress.</p><p>Overall, these studies demonstrate cardiac oxidative stress, in particular, GSH depletion, plays an important role in progression of cardiovascular dysfunction.</p> 2008-03-18 English text The Ohio State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=osu1203478009 http://rave.ohiolink.edu/etdc/view?acc_num=osu1203478009 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic Pharmacology
cardiovascular
diabetes
oxidative stress
glutathione
cocaine
spellingShingle Pharmacology
cardiovascular
diabetes
oxidative stress
glutathione
cocaine
Han, Bing
Mechanistic Consequences of Cardiac Oxidative Stress
author Han, Bing
author_facet Han, Bing
author_sort Han, Bing
title Mechanistic Consequences of Cardiac Oxidative Stress
title_short Mechanistic Consequences of Cardiac Oxidative Stress
title_full Mechanistic Consequences of Cardiac Oxidative Stress
title_fullStr Mechanistic Consequences of Cardiac Oxidative Stress
title_full_unstemmed Mechanistic Consequences of Cardiac Oxidative Stress
title_sort mechanistic consequences of cardiac oxidative stress
publisher The Ohio State University / OhioLINK
publishDate 2008
url http://rave.ohiolink.edu/etdc/view?acc_num=osu1203478009
work_keys_str_mv AT hanbing mechanisticconsequencesofcardiacoxidativestress
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