Download the full-sized PDF of The role of cytochrome P450 derived arachidonic acid metabolites against Angiotensin II-induced cardiac hypertrophy in Sprague Dawley rats and the RL-14 cell lineDownload the full-sized PDF



Permanent link (DOI):


Export to: EndNote  |  Zotero  |  Mendeley


This file is in the following communities:

Graduate Studies and Research, Faculty of


This file is in the following collections:

Theses and Dissertations

The role of cytochrome P450 derived arachidonic acid metabolites against Angiotensin II-induced cardiac hypertrophy in Sprague Dawley rats and the RL-14 cell line Open Access


Other title
Cardiac hypertrophy
Cytochrome P450
Arachidonic acid
Type of item
Degree grantor
University of Alberta
Author or creator
Elkhatali, Samya
Supervisor and department
El-Kadi, Ayman (Faculty of pharmacy and pharmaceutical sciences)
Examining committee member and department
Brocks, Dion (Faculty of pharmacy and pharmaceutical sciences)
Baker, Glen (Department of psychiatry)
Faculty of Pharmacy and Pharmaceutical Sciences
Pharmaceutical Sciences
Date accepted
Graduation date
Master of Science
Degree level
Several cytochrome P450 (CYP) enzymes and their arachidonic acid (AA) metabolites play essential roles in the maintenance of cardiovascular health, and their alteration gives rise to a number of cardiovascular diseases, including cardiac hypertrophy and heart failure. Recent data demonstrated that 19-hydroxyeicosatetraenoic acid (19-HETE) is the major subterminal-HETE in the heart tissue and its formation is decreased during cardiac hypertrophy, while in contrast that of mid-chain HETEs increased. Therefore, our aims were; 1) to examine whether 19-HETE confers cardioprotection against angiotensin II (Ang II)-induced cardiac hypertrophy at in vitro and in vivo levels in which isoniazid (INH) was used to increase 19-HETE formation in vivo, and 2) to study the cardioprotective effect of inhibiting the formation of midchain HETEs [using 2,3',4,5'-tetramethoxystilbene (TMS)] against Ang II-induced cardiac hypertrophy also at in vitro and in vivo levels. Our results demonstrated that 19-HETE conferred a cardioprotective effect against Ang II-induced cellular hypertrophy, as indicated by the significant reduction in the β/α-MHC ratio. Echocardiographic analysis showed that INH improved heart dimensions, in addition to reversing the increase in heart weight to tibial length ratio caused by Ang II. The cardioprotective effect of INH was associated with an increased level of cardiac 19-HETE. Additionally, INH significantly reduced levels of the cardiotoxic AA metabolite 20-HETE-induced by Ang II treatment. Likewise, we demonstrated that TMS protected against Ang II-induced cardiac hypertrophy as indicated by echocardiography and heart weight to tibia length ratio. TMS significantly reduced the β/α-MHC ratio. In addition, this cardioprotective effect of TMS was associated with decreased levels of cardiac mid-chain and 20-HETE as well as significantly reducing AA levels. TMS decreased oxidative stress, inhibiting the phosphorylation of ERK1/2, p38 MAPK and the binding of p65 NF-κB. In conclusion, our results demonstrate that both INH and TMS partially protect against Ang II-induced cardiac hypertrophy through manipulating the levels of AA metabolites. This further confirms the role of CYPs, and their associated AA metabolites, in the development of cardiac hypertrophy.
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
Citation for previous publication

File Details

Date Uploaded
Date Modified
Audit Status
Audits have not yet been run on this file.
File format: pdf (PDF/A)
Mime type: application/pdf
File size: 3164948
Last modified: 2016:06:24 17:45:32-06:00
Filename: Elkhatali_Samya_201509_MSc.pdf
Original checksum: d4608d0998cccaf5ee97fd96775c68f5
Activity of users you follow
User Activity Date