期刊
HAEMATOLOGICA
卷 100, 期 7, 页码 870-880出版社
FERRATA STORTI FOUNDATION
DOI: 10.3324/haematol.2015.124586
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- PRIN [201228PNX83_003]
- FUR_UNIVR
The anemia of sickle cell disease is associated with a severe inflammatory vasculopathy and endothelial dysfunction, which leads to painful and life-threatening clinical complications. Growing evidence supports the anti-inflammatory properties of omega-3 fatty acids in clinical models of endothelial dysfunction. Promising but limited studies show potential therapeutic effects of omega-3 fatty acid supplementation in sickle cell disease. Here, we treated humanized healthy and sickle cell mice for 6 weeks with omega-3 fatty acid diet (fish-oil diet). We found that a omega-3 fatty acid diet: (i) normalizes red cell membrane omega-6/omega-3 ratio; (ii) reduces neutrophil count; (iii) decreases endothelial activation by targeting endothelin-1 and (iv) improves left ventricular outflow tract dimensions. In a hypoxia-reoxygenation model of acute vaso-occlusive crisis, a omega-3 fatty acid diet reduced systemic and local inflammation and protected against sickle cell-related end-organ injury. Using isolated aortas from sickle cell mice exposed to hypoxia-reoxygenation, we demonstrated a direct impact of a omega-3 fatty acid diet on vascular activation, inflammation, and anti-oxidant systems. Our data provide the rationale for omega-3 dietary supplementation as a therapeutic intervention to reduce vascular dysfunction in sickle cell disease.
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