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Splenocyte microvesicles are pro-senescent endothelial effectors : impact of age and protection by EPA/DHA 6/1, an optimized formulation of nutritional eicosapentaenoic and docosahexaenoic polyunsaturated fatty acids

Abstract : Ageing is associated with progressive endothelial senescence favoring endothelial and vascular dysfunction, often associated with cardiovascular diseases. We investigated in young, middle-aged and old rats (Y, MA, O) the impact of ageing on the shedding of spleen-derived leukocytes microvesicles (SMVs) and measured their pro-senescent effects in porcine primary coronary artery endothelial cells (ECs). Oxidative stress accumulates in spleen tissue and SMVs shedding increases with age. SMVs from MA, O but not Y rats induced premature endothelial senescence, with increased Senescence-Associated-β-galactosidase activity and up-regulated p53, p21, p16. SMVs shifted ECs towards a pro-inflammatory and pro-atherothrombotic phenotype with increased endothelial oxidative stress and down-regulated eNOS. Short-term intake of omega-3 EPA:DHA 6:1 but not EPA:DHA 1:1 reduced age-related oxidative stress and SMVs shedding in MA and O spleen tissues, and abolished SMVs-induced premature endothelial senescence in MA, most probably by reducing oxidative stress and preventing the activation of the local angiotensin system.
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Abdul Wahid Qureshi. Splenocyte microvesicles are pro-senescent endothelial effectors : impact of age and protection by EPA/DHA 6/1, an optimized formulation of nutritional eicosapentaenoic and docosahexaenoic polyunsaturated fatty acids. Pharmacology. Université de Strasbourg, 2019. English. ⟨NNT : 2019STRAJ077⟩. ⟨tel-02901570⟩

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