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Maternal omega-3 PUFA supplementation prevents hyperoxia-induced pulmonary hypertension in the offspring

Abstract : Pulmonary hypertension (PH) and right ventricular hypertrophy (RVH) affect 16-25% of premature infants with bronchopulmonary dysplasia (BPD), contributing significantly to perinatal morbidity and mortality. Omega-3 polyunsaturated fatty acids (PUFA omega-3) can improve vascular remodeling, angiogenesis, and inflammation under pathophysiological conditions. However, the effects of PUFA omega-3 supplementation in BPD-associated PH are unknown. The present study aimed to evaluate the effects of PUFA omega-3 on pulmonary vascular remodeling, angiogenesis, and inflammatory response in a hyperoxia-induced rat model of PH. From embryonic day 15, pregnant Sprague-Dawley rats were supplemented daily with PUFA omega-3, PUFA omega-6, or normal saline (0.2 ml/day). After birth, pups were pooled, assigned as 12 per litter, randomly assigned to either air or continuous oxygen exposure (fraction of inspired oxygen = 85%) for 20 days, and then euthanized for pulmonary hemodynamic and morphometric analysis. We found that PUFA omega-3 supplementation improved survival, decreased right ventricular systolic pressure and RVH caused by hyperoxia, and significantly improved alveolarization, vascular remodeling, and vascular density. PUFA omega-3 supplementation produced a higher level of total omega-3 in lung tissue and breast milk and was found to reverse the reduced levels of VEGFA, VEGF receptor 2, angiopoietin-1 (ANGPT1), endothelial TEK tyrosine kinase, endothelial nitric oxide synthase, and nitric oxide concentrations in lung tissue and the increased ANGPT2 levels in hyperoxia-exposed rats. The beneficial effects of PUFA omega-3 in improving lung injuries were also associated with an inhibition of leukocyte infiltration and reduced expression of the proinflammatory cytokines IL-1 beta, IL-6, and TNF-alpha. These data indicate that maternal PUFA omega-3 supplementation strategies could effectively protect against infant PH induced by hyperoxia.
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Submitted on : Monday, October 1, 2018 - 2:17:00 PM
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Ying Zhong, Daniel D. Catheline, Ali Houeijeh, Dyuti Sharma, Lizhong Du, et al.. Maternal omega-3 PUFA supplementation prevents hyperoxia-induced pulmonary hypertension in the offspring. American Journal of Physiology - Lung Cellular and Molecular Physiology, American Physiological Society, 2018, 315 (1), pp.L116 - L132. ⟨10.1152/ajplung.00527.2017⟩. ⟨hal-01884844⟩



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