Myeloid atg5 deletion impairs n-3 PUFA-mediated atheroprotection.
Atherosclerosis
; 295: 8-17, 2020 02.
Article
em En
| MEDLINE
| ID: mdl-31978760
ABSTRACT
BACKGROUND AND AIMS:
Dietary long-chain (≥20 carbons) n-3 polyunsaturated fatty acids (PUFAs) reduce atherosclerosis and enhance macrophage autophagy activation. How macrophage autophagy impacts atherosclerotic progression, particularly when comparing dietary n-3 PUFA supplementation vs. saturated fat feeding, is unknown.METHODS:
We generated myeloid-specific autophagy-deficient and control mice in the Ldlr-/- background by transplanting bone marrow from myeloid-specific autophagy-related (atg) 5 knockout mice and wild type controls into irradiated Ldlr-/- recipients. After 7 weeks for recovery from radiation, mice were fed an atherogenic diet containing 0.2% cholesterol and 20% calories as palm oil (PO diet), or 10% calories as PO plus 10% calories as fish oil (FO diet) for 16 weeks.RESULTS:
Compared to PO, FO significantly reduced plasma cholesterol, triglyceride, hepatic neutral lipid, and aortic caspase-1 cleavage, but increased aortic efferocytosis, leading to attenuated atherosclerosis in Ldlr-/- mice receiving wild type bone marrow. Myeloid atg5 deletion had little impact on plasma lipid concentrations and hepatic neutral lipid content, regardless of diet. Myeloid atg5 deletion increased aortic caspase-1 cleavage, decreased aortic efferocytosis and worsened atherosclerosis only in the FO-fed Ldlr-/- mice.CONCLUSIONS:
Deficient myeloid autophagy significantly attenuated FO-induced atheroprotection, suggesting that dietary n-3 PUFAs reduce atherosclerosis, in part, by activation of macrophage autophagy.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ácidos Graxos Ômega-3
/
Aterosclerose
/
Proteína 5 Relacionada à Autofagia
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article