Abstract |
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 ω-3 fatty acids in clinical models of endothelial dysfunction. Promising but limited studies show potential therapeutic effects of ω-3 fatty acid supplementation in sickle cell disease. Here, we treated humanized healthy and sickle cell mice for 6 weeks with ω-3 fatty acid diet ( fish-oil diet). We found that a ω-3 fatty acid diet: (i) normalizes red cell membrane ω-6/ω-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 ω-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 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 intervention to reduce vascular dysfunction in sickle cell disease.
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Authors | Brian T Kalish, Alessandro Matte, Immacolata Andolfo, Achille Iolascon, Olga Weinberg, Alessandra Ghigo, James Cimino, Angela Siciliano, Emilio Hirsch, Enrica Federti, Mark Puder, Carlo Brugnara, Lucia De Franceschi |
Journal | Haematologica
(Haematologica)
Vol. 100
Issue 7
Pg. 870-80
(Jul 2015)
ISSN: 1592-8721 [Electronic] Italy |
PMID | 25934765
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright© Ferrata Storti Foundation. |
Chemical References |
- Anti-Inflammatory Agents
- Endothelin-1
- Fatty Acids, Omega-3
- Oxygen
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Topics |
- Anemia, Sickle Cell
(diet therapy, metabolism, pathology)
- Animals
- Anti-Inflammatory Agents
(pharmacology)
- Blood Vessels
(drug effects, metabolism, pathology)
- Dietary Supplements
- Disease Models, Animal
- Endothelin-1
(antagonists & inhibitors, biosynthesis)
- Endothelium, Vascular
(drug effects, metabolism, pathology)
- Erythrocyte Membrane
(drug effects, pathology)
- Fatty Acids, Omega-3
(pharmacology)
- Humans
- Hypoxia
(diet therapy, metabolism, pathology)
- Mice
- Mice, Transgenic
- Neutrophils
(drug effects, metabolism, pathology)
- Oxygen
(adverse effects)
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