Skip to Main content Skip to Navigation
Theses

Influence de l'acide eicosapentaénoïque sur l'activité cardiaque et sa modulation par le stress oxydant - Perspectives pour l'obésité et l'endocardite aigüe humaines

Abstract : Cardiovascular disease is the leading cause of death in the world. Many situations trigger heart failure which is usually associated with mitochondrial dysfunction. Oxidative stress is a major contributor to these dysfunctions. Polyunsaturated fatty acids of the 3 family, in particular EPA, have often been associated with cardioprotective effects, but in some cases their impact is deleterious. The hypothesis behind this thesis is that EPA becomes harmful in situations in which the oxidative stress is too high: an appropriate combination with an antioxidant would maintain the cardio-protective properties. Several models of pathological situations characterized by a low or severe and chronic oxidative stress were studied. EPA displays beneficial effects on the heart by modulating collagen, coronary reactivity, mitochondrial function, oxidative status, inflammation, energy metabolism, calcium homeostasis and lipid profile. However, in case of a high and chronic oxidative stress triggered by diabetes mellitus and an obesogenic diet, EPA results in a dramatic increase in animal mortality. This effect is countered by enriching the diet with green tea extract thanks to the antioxidant and lipid-lowering properties of this last. The combination of EPA with an antioxidant adapted to the situation and administered in adequate doses is essential when the oxidative stress is severe enough to induce lipid peroxidation. The beneficial impact of EPA is related to mitochondrial actors such as SOD2, UCP3 and Sirt3. The findings obtained in these animal studies need to be verified in humans to determine whether the cardioprotective effect of EPA combined with an antioxidant is maintained. This thesis also describes a reliable method allowing the extraction of human cardiac mitochondria from atrial rejection obtained during extracorporeal circulation. Omic studies on the plasma would also allow the discovery of new biomarkers of mitochondrial function permitting clinicians to highlight possible dysfunctions prior to onset of the heart failure and to adapt a precocious treatment to the particular patient situation.
Complete list of metadatas

Cited literature [869 references]  Display  Hide  Download

https://tel.archives-ouvertes.fr/tel-02498460
Contributor : Abes Star :  Contact
Submitted on : Wednesday, March 4, 2020 - 2:51:09 PM
Last modification on : Tuesday, March 17, 2020 - 3:30:56 AM
Long-term archiving on: : Friday, June 5, 2020 - 2:16:10 PM

File

2019CLFAS012_LEGER.pdf
Version validated by the jury (STAR)

Identifiers

  • HAL Id : tel-02498460, version 1

Collections

Citation

Thibault Leger. Influence de l'acide eicosapentaénoïque sur l'activité cardiaque et sa modulation par le stress oxydant - Perspectives pour l'obésité et l'endocardite aigüe humaines. Cardiologie et système cardiovasculaire. Université Clermont Auvergne, 2019. Français. ⟨NNT : 2019CLFAS012⟩. ⟨tel-02498460⟩

Share

Metrics

Record views

149

Files downloads

312