Van Hoose 2015 Thesis

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Van Hoose P (2015) Co-treatment with conjugated linoleic acid and nitrite modulates mitochondrial respiration and electron transport chain activity in vivo and attenuates mitochondrial dysfunction during cardiac injury. Dissertations p128.

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Van Hoose P (2015) Dissertation

Abstract: Cardiovascular disease and subsequent complications, such as myocardial infarction (MI), is the leading cause of death within the United States. Clinical intervention to reduce cardiac damage following myocardial ischemia is limited. Polyunsaturated fatty acids have been linked to an overall beneficial effect on cardiovascular health and function. Conjugated linoleic acid (cLA) is an 18:2 unsaturated fatty acid found within the diet in ruminant meat and dairy products. The cis-9 trans-11 isomer of cLA is the most prominent isomer within the diet and cLA has been linked to favorable outcomes in numerous disease states. The mechanism mediating the effects of cLA are still unclear but mitochondria appear to be playing a prominent role. Nitrite (NO2-) is a dietary source of nitric oxide (NO), as it is found within green leafy vegetables and it is linked to cardioprotection in ischemia reperfusion injury models. Alterations in mitochondrial function and electron transport chain enzymatic activity have been elucidated as the mechanisms mediating nitrite cardioprotection. However, recent clinical trials have reported no positive outcome in patients undergoing MI who have been supplemented with nitrite. A combination treatment of cLA and nitrite preserves cardiac function following MI, highlighting that the interaction between dietary constituents may influence cardioprotective effects. In the first step of this study, we examine whether the combination treatment of cLA and nitrite influenced mitochondrial respiration and electron transport chain activity under baseline conditions. In the second step of this study, we examine the impact of co-treatment with cLA and nitrite on mitochondrial function following MI and aging. Under baseline conditions, we found that co-administration of cLA and nitrite decreased mitochondrial respiration and complex III activity. Following MI, the co-treatment of cLA and nitrite attenuated MI-induced increases in mitochondrial respiration, complex III activity, and hydrogen peroxide levels. However, following aging the co-treatment was unable to restore aging induced mitochondrial dysfunction. These results demonstrate that in combination the dietary constituents, cLA and nitrite, are able to influence mitochondrial function under non-injury setting and following MI. Overall, this supports a role of mitochondria in the cardioprotective effects mediated by a combination treatment of cLA and nitrite.

Keywords: Amplex Red

Labels: MiParea: Respiration, Exercise physiology;nutrition;life style, mt-Medicine, Pharmacology;toxicology  Pathology: Cardiovascular  Stress:Ischemia-reperfusion  Organism: Mouse  Tissue;cell: Heart  Preparation: Isolated mitochondria  Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase 

Coupling state: LEAK, OXPHOS, ET 

HRR: Oxygraph-2k