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Les peptides mimétiques de la Thiorédoxine-1 : nouvelle stratégie thérapeutique pour les maladies cardiovasculaires

Abstract : Oxidative stress and inflammation play a pathogenic role in atherosclerosis. Thioredoxin-1 (Trx-1) is an anti-oxidative, anti-inflammatory protein with atheroprotective effects. However, in vivo cleavage of Trx-1 generates a truncated pro-inflammatory protein, Trx-80, which compromises the therapeutic use of Trx-1. The aim of my thesis is to characterize a new therapeutic strategy based on Trx-mimetic peptides (TxMP) for the treatment of atherosclerosis. We synthesized a small peptide based on the active site of Trx-1 named CB3. Firstly, CB3 was validated on cultured peritoneal murine macrophages (cellular viability, anti-oxidant and anti-inflammatory responses). Secondly, the atherosclerotic mouse model (ApoE2.Ki) fed a high fat diet was intraperitoneally injected with CB3 to measure their anti-oxidant, anti-inflammatory and anti-atherogenic effects. Our results clearly showed that, similar to the full length Trx-1, CB3 exerts protective effects by reducing inflammation and oxidative stress in macrophages and in ApoE.Ki mice. The atheroprotective effect of CB3 opens promising therapeutic approaches for treatment of atherosclerosis.
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Fanny Canesi. Les peptides mimétiques de la Thiorédoxine-1 : nouvelle stratégie thérapeutique pour les maladies cardiovasculaires. Médecine humaine et pathologie. Sorbonne Université, 2018. Français. ⟨NNT : 2018SORUS500⟩. ⟨tel-02613771⟩

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