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case1258128805.pdf (1.06 MB)
ETD Abstract Container
Abstract Header
Omega-3 Fatty Acids and Heart Failure
Author Info
O'Shea, Karen Michelle
Permalink:
http://rave.ohiolink.edu/etdc/view?acc_num=case1258128805
Abstract Details
Year and Degree
2010, Doctor of Philosophy, Case Western Reserve University, Nutrition.
Abstract
Observations of cardioprotection with ω-3 polyunsaturated fatty acids (ω-3 PUFA) are common, but the mechanisms responsible are unclear. Left ventricular (LV) dysfunction is associated with impaired mitochondria and reduced oxidative capacity in heart failure, but the effects of ω-3 PUFA on mitochondria have not been well-characterized. In addition, elevated circulating adiponectin is a result of ω-3 PUFA supplementation and is associated with preserved LV function in response to pressure overload. The goal of this dissertation is to assess the potential mechanisms responsible for the effects of ω-3 PUFA on the progression to heart failure. In this dissertation, studies were performed where heart failure was generated in rats by coronary artery ligation. Sham and heart failure rats were fed a standard chow (STD) or ω-3 PUFA chow, EPA+DHA, for 12 weeks. EPA+DHA did not prevent LV remodeling in response to infarction, but EPA+DHA treatment significantly altered mitochondrial membrane composition in all rats and delayed calcium-induced mitochondrial permeability transition pore opening in sham rats, which has been implicated in the development and progression of heart failure. The next study focused on the role of adiponectin in mediating the effects of EPA+DHA. Adiponectin-/- and wild type (WT) mice were subjected to transverse aortic constriction (TAC) to induce cardiac hypertrophy and heart failure, and fed STD or EPA+DHA for 6 weeks. Adiponectin deletion prevented LV expansion, preserved ejection fraction, and maintained mitochondrial enzyme activities compared to WT mice subjected to TAC, indicating that adiponectin is not cardioprotective in response to pressure overload. EPA+DHA also blunted LV dilation and preserved mitochondrial enzyme activities compared to mice fed STD on a WT background. There were no effects of EPA+DHA in adiponectin-/- mice, suggesting that adiponectin may not mediate the effects of EPA+DHA. In conlusion, EPA+DHA supplementation exerts cardioprotection in a model-dependent manner. Dietary EPA+DHA yields profound changes in cardiac membranes, delays MPTP opening in normal rats, and offers protection against pressure overload in mice but not against myocardial infarction in rats. These results indicate that EPA+DHA may be beneficial in cases of pressure overload, but not myocardial infarction.
Committee
William Stanley, PhD (Advisor)
Edith Lerner, PhD (Committee Chair)
Danny Manor, PhD (Committee Member)
Alison Steiber, PhD (Committee Member)
Margaret Chandler, PhD (Committee Member)
Pages
142 p.
Subject Headings
Nutrition
Keywords
heart failure
;
omega-3 polyunsaturated fatty acids
;
adiponectin
;
mitochondria
Recommended Citations
Refworks
EndNote
RIS
Mendeley
Citations
O'Shea, K. M. (2010).
Omega-3 Fatty Acids and Heart Failure
[Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1258128805
APA Style (7th edition)
O'Shea, Karen.
Omega-3 Fatty Acids and Heart Failure.
2010. Case Western Reserve University, Doctoral dissertation.
OhioLINK Electronic Theses and Dissertations Center
, http://rave.ohiolink.edu/etdc/view?acc_num=case1258128805.
MLA Style (8th edition)
O'Shea, Karen. "Omega-3 Fatty Acids and Heart Failure." Doctoral dissertation, Case Western Reserve University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=case1258128805
Chicago Manual of Style (17th edition)
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Document number:
case1258128805
Download Count:
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Copyright Info
© 2009, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.