0396 : Prebiotics supplementation improves the endothelial dysfunction induced by a nutritional deficiency in n-3 polyunsaturated fatty acids (PUFA)

Abstract

Nutritional disorders are associated with a high risk of developing cardiovascular diseases, endothelial dysfunction being an early key marker. We have demonstrated that metabolic alterations induced by a nutritional depletion in n-3 PUFA are improved by a supplementation in prebiotics (non-digestible fructans). The present work focusses on the impact of prebiotics on the endothelial dysfunction induced by the n-3 PUFA depletion in ApoE –/– mice model. C57Bl/6J (WT) and ApoE –/– (KO) mice were fed a n-3 PUFA depleted-diet (DEF) for 12 weeks. For the last fifteen days, mice were or not supplemented with prebiotics (PRE). The vascular morphology and function were evaluated in first, second and third order mesenteric arteries by histology and wire myograph. Micro-arteries from KO DEF PRE mice develop an increased basal tone and present a larger vessel diameter, compared to vessels from non-supplemented mice. The PRE supplementation in KO DEF mice leads to an increased media thickness in first order mesenteric arteries, this is even higher in the second order branch, in comparison to non-supplemented mice. KO DEF PRE micro-arteries contract significantly more in response to a KCl challenge than vessels from non-supplemented mice. As expected micro-arteries from KO DEF mice present an endothelial dysfunction after 12 weeks of n-3 PUFA depletion with a significant decrease of endothelial-dependent relaxation in comparison to WT DEF arteries. The PRE supplementation is able to improve the endothelial function by restoring the endothelial-dependent relaxation in arteries from KO DEF mice. We point out fructan-type prebiotics as a potential therapeutic tool in endothelial dysfunction. Our results argue in favor of an outward muscular remodeling in mesenteric arteries, leading to an increased blood flow and a better vascular reactivity. The results on endothelial function evoke an important implication of the nitric oxide pathway in this phenomenon.