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Haematologica. 2015 Jul;100(7):870-80. doi: 10.3324/haematol.2015.124586. Epub 2015 May 1.

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

Author information

1
Department of Surgery and The Vascular Biology Program, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
2
Department of Medicine, University of Verona-AOUI Verona, Policlinico GB Rossi, Verona, Italy.
3
Department of Biochemistry, University Federico II, Naples, Italy.
4
Departments of Pathology and Laboratory Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
5
Molecular Biotechnology Center and Department of Molecular Biotechology and Health Science, University of Turin, Italy.
6
Departments of Pathology and Laboratory Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA carlo.brugnara@childrens.harvard.edu.

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.

PMID:
25934765
PMCID:
PMC4486221
DOI:
10.3324/haematol.2015.124586
[Indexed for MEDLINE]
Free PMC Article

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