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.
journal_name
Atherosclerosisjournal_title
Atherosclerosisauthors
Wang Z,Sequeira RC,Zabalawi M,Madenspacher J,Boudyguina E,Ou T,Nelson JM,Nie Y,Zhao Q,Fessler MB,Zhu Xdoi
10.1016/j.atherosclerosis.2020.01.004subject
Has Abstractpub_date
2020-02-01 00:00:00pages
8-17eissn
0021-9150issn
1879-1484pii
S0021-9150(20)30020-4journal_volume
295pub_type
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