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ANGIOTENSIN-(1-7) FOR THE TARGETED TREATMENT OF DOXORUBICIN-INDUCED CARDIOTOXICITY IN JUVENILE RATS

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abstract
Advances in chemotherapies led to increased life expectancy and improved outcomes in cancer patients. However, treatment-related cardiotoxicity is a continuing issue in survivors. Doxorubicin (Dox) is an effective anthracycline chemotherapy that can produce a dose-dependent cardiotoxicity manifesting as cardiac dysfunction leading to heart failure (HF). Cardiotoxicity management involves monitoring each patient before and during therapy as well as long-term follow-up. In 1995, the FDA approved dexrazoxane as a cardioprotectant to prevent Dox-induced cardiotoxicity; however, a lack of mechanistic understanding and an associated increase in secondary malignancies prompted the FDA to only grant approval for use to a subset of adult patients and excluded administration to pediatric patients. Therefore, there is a need to develop an effective and safe cardioprotectant for pediatric patients receiving Dox as part of their chemotherapeutic regimen. The purpose of the studies described in this dissertation were to determine whether angiotensin-(1-7) [Ang-(1-7)], a peptide hormone of the renin-angiotensin system (RAS) with cardioprotective properties, prevents cardiotoxicity in a clinically relevant Dox treatment of juvenile rodents.
subject
Angiotensin-(1-7)
Anthracycline
Cardiotoxicity
Doxorubicin
Juvenile
Treatment
contributor
Rahimi, Omeed (author)
Gallagher, Patricia E (committee chair)
Gallagher, Patricia E (committee member)
Tallant, Elisabeth A (committee member)
Jordan, James E (committee member)
Varagic, Jasmina (committee member)
Pardee, Timothy S (committee member)
date
2019-05-24T08:35:44Z (accessioned)
2020-05-23T08:30:20Z (available)
2019 (issued)
degree
Physiology and Pharmacology (discipline)
embargo
2020-05-23 (terms)
identifier
http://hdl.handle.net/10339/93952 (uri)
language
en (iso)
publisher
Wake Forest University
title
ANGIOTENSIN-(1-7) FOR THE TARGETED TREATMENT OF DOXORUBICIN-INDUCED CARDIOTOXICITY IN JUVENILE RATS
type
Dissertation

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