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Dietary ω-3 fatty acids protect against vasculopathy in a transgenic mouse model of sickle cell disease.
Haematologica. 2015 Jul; 100(7):870-80.H

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+Show Affiliations

Kalish BT
Department of Surgery and The Vascular Biology Program, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Matte A
Department of Medicine, University of Verona-AOUI Verona, Policlinico GB Rossi, Verona, Italy.
Andolfo I
Department of Biochemistry, University Federico II, Naples, Italy.
Iolascon A
Department of Biochemistry, University Federico II, Naples, Italy.
Weinberg O
Departments of Pathology and Laboratory Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Ghigo A
Molecular Biotechnology Center and Department of Molecular Biotechology and Health Science, University of Turin, Italy.
Cimino J
Molecular Biotechnology Center and Department of Molecular Biotechology and Health Science, University of Turin, Italy.
Siciliano A
Department of Medicine, University of Verona-AOUI Verona, Policlinico GB Rossi, Verona, Italy.
Hirsch E
Molecular Biotechnology Center and Department of Molecular Biotechology and Health Science, University of Turin, Italy.
Federti E
Department of Medicine, University of Verona-AOUI Verona, Policlinico GB Rossi, Verona, Italy.
Puder M
Department of Surgery and The Vascular Biology Program, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Brugnara C
Departments of Pathology and Laboratory Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA carlo.brugnara@childrens.harvard.edu.
De Franceschi L
Department of Medicine, University of Verona-AOUI Verona, Policlinico GB Rossi, Verona, Italy.

MeSH

Anemia, Sickle CellAnimalsAnti-Inflammatory AgentsBlood VesselsDietary SupplementsDisease Models, AnimalEndothelin-1Endothelium, VascularErythrocyte MembraneFatty Acids, Omega-3HumansHypoxiaMiceMice, TransgenicNeutrophilsOxygen

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25934765

Citation

Kalish, Brian T., et al. "Dietary Ω-3 Fatty Acids Protect Against Vasculopathy in a Transgenic Mouse Model of Sickle Cell Disease." Haematologica, vol. 100, no. 7, 2015, pp. 870-80.
Kalish BT, Matte A, Andolfo I, et al. Dietary ω-3 fatty acids protect against vasculopathy in a transgenic mouse model of sickle cell disease. Haematologica. 2015;100(7):870-80.
Kalish, B. T., Matte, A., Andolfo, I., Iolascon, A., Weinberg, O., Ghigo, A., Cimino, J., Siciliano, A., Hirsch, E., Federti, E., Puder, M., Brugnara, C., & De Franceschi, L. (2015). Dietary ω-3 fatty acids protect against vasculopathy in a transgenic mouse model of sickle cell disease. Haematologica, 100(7), 870-80. https://doi.org/10.3324/haematol.2015.124586
Kalish BT, et al. Dietary Ω-3 Fatty Acids Protect Against Vasculopathy in a Transgenic Mouse Model of Sickle Cell Disease. Haematologica. 2015;100(7):870-80. PubMed PMID: 25934765.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dietary ω-3 fatty acids protect against vasculopathy in a transgenic mouse model of sickle cell disease. AU - Kalish,Brian T, AU - Matte,Alessandro, AU - Andolfo,Immacolata, AU - Iolascon,Achille, AU - Weinberg,Olga, AU - Ghigo,Alessandra, AU - Cimino,James, AU - Siciliano,Angela, AU - Hirsch,Emilio, AU - Federti,Enrica, AU - Puder,Mark, AU - Brugnara,Carlo, AU - De Franceschi,Lucia, Y1 - 2015/05/01/ PY - 2015/02/02/received PY - 2015/04/27/accepted PY - 2015/5/3/entrez PY - 2015/5/3/pubmed PY - 2016/2/10/medline SP - 870 EP - 80 JF - Haematologica JO - Haematologica VL - 100 IS - 7 N2 - 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. SN - 1592-8721 UR - https://www.unboundmedicine.com/medline/citation/25934765/Dietary_ω_3_fatty_acids_protect_against_vasculopathy_in_a_transgenic_mouse_model_of_sickle_cell_disease_ DB - PRIME DP - Unbound Medicine ER -