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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)870-880
Number of pages11
JournalHaematologica
Volume100
Issue number7
DOIs
StatePublished - Jul 6 2015
Externally publishedYes

ASJC Scopus subject areas

  • Hematology

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