Efficient megakaryopoiesis and platelet production require phospholipid remodeling and PUFA uptake through CD36.
Nat Cardiovasc Res
; 2(8): 746-763, 2023 Aug.
Article
em En
| MEDLINE
| ID: mdl-39195958
ABSTRACT
Lipids contribute to hematopoiesis and membrane properties and dynamics; however, little is known about the role of lipids in megakaryopoiesis. Here we show that megakaryocyte progenitors, megakaryocytes and platelets present a unique lipidome progressively enriched in polyunsaturated fatty acid (PUFA)-containing phospholipids. In vitro, inhibition of both exogenous fatty acid functionalization and uptake as well as de novo lipogenesis impaired megakaryocyte differentiation and proplatelet production. In vivo, mice on a high saturated fatty acid diet had significantly lower platelet counts, which was prevented by eating a PUFA-enriched diet. Fatty acid uptake was largely dependent on CD36, and its deletion in mice resulted in low platelets. Moreover, patients with a CD36 loss-of-function mutation exhibited thrombocytopenia and increased bleeding. Our results suggest that fatty acid uptake and regulation is essential for megakaryocyte maturation and platelet production and that changes in dietary fatty acids may be a viable target to modulate platelet counts.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fosfolipídeos
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Plaquetas
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Megacariócitos
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Antígenos CD36
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Trombopoese
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Ácidos Graxos Insaturados
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Nat Cardiovasc Res
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos