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

Area of Science:

• Neonatology
• Pulmonary Medicine
• Nutritional Science

Background:

• Bronchopulmonary dysplasia (BPD) in premature infants is linked to significant morbidity and mortality from pulmonary hypertension (PH) and right ventricular hypertrophy (RVH).
• Omega-3 polyunsaturated fatty acids (PUFA ω-3) demonstrate potential in modulating vascular remodeling, angiogenesis, and inflammation in various pathophysiological contexts.
• The efficacy of PUFA ω-3 supplementation in mitigating BPD-associated PH remains largely unexplored.

Purpose of the Study:

• To investigate the protective effects of maternal PUFA ω-3 supplementation against hyperoxia-induced PH and pulmonary vascular remodeling in a rat model.
• To assess the impact of PUFA ω-3 on angiogenesis, inflammation, and key molecular markers in the lungs of offspring exposed to hyperoxia.

Main Methods:

• Pregnant Sprague-Dawley rats received daily PUFA ω-3, PUFA ω-6, or saline from embryonic day 15.
• Pups were exposed to 85% oxygen from birth for 20 days, followed by pulmonary hemodynamic and morphometric analysis.
• Lung tissue and breast milk were analyzed for PUFA ω-3 levels, angiogenic factors (VEGF, ANGPTs), nitric oxide, and inflammatory markers (cytokines, leukocyte infiltration).

Main Results:

• PUFA ω-3 supplementation improved pup survival, reduced hyperoxia-induced right ventricular systolic pressure and RVH.
• Significant improvements were observed in alveolarization, pulmonary vascular remodeling, and vascular density in PUFA ω-3 supplemented groups.
• PUFA ω-3 reversed altered levels of VEGFA, VEGF receptor 2, ANGPT1, endothelial TEK tyrosine kinase, endothelial nitric oxide synthase, and nitric oxide, while decreasing ANGPT2, IL-1β, IL-6, and TNF-α, and inhibiting leukocyte infiltration.

Conclusions:

• Maternal PUFA ω-3 supplementation offers a promising protective strategy against infant PH associated with bronchopulmonary dysplasia.
• This nutritional intervention effectively ameliorates pulmonary vascular remodeling and inflammation in a hyperoxia-induced PH model.
• PUFA ω-3 supplementation positively influences key angiogenic and inflammatory pathways, supporting lung development and function in vulnerable infants.