Dietary w-3 fatty acids protect against vasculopathy in a transgenic mouse model for sickle cell disease.

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-inflammatoryproperties of ω-3 fatty acids in clinical models of endothelial dysfunction. Promising but limited studiesshow potential therapeutic effects of ω-3 fatty acid supplementation in sickle cell disease. Here, we treated humanizedhealthy and sickle cell mice for 6 weeks with ω-3 fatty acid diet (fish-oil diet). We found that a ω-3 fatty aciddiet: (i) normalizes red cell membrane ω-6/ ω-3 ratio; (ii) reduces neutrophil count; (iii) decreases endothelial activationby targeting endothelin-1 and (iv) improves left ventricular outflow tract dimensions. In a hypoxia-reoxygenationmodel of acute vaso-occlusive crisis, a ω-3 fatty acid diet reduced systemic and local inflammation andprotected 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 ω-3 fatty acid diet on vascular activation, inflammation,and anti-oxidant systems. Our data provide the rationale for ω-3 dietary supplementation as a therapeutic interventionto reduce vascular dysfunction in sickle cell disease.