| First Author | Wang Z | Year | 2020 |
| Journal | Atherosclerosis | Volume | 295 |
| Pages | 8-17 | PubMed ID | 31978760 |
| Mgi Jnum | J:303370 | Mgi Id | MGI:6512121 |
| Doi | 10.1016/j.atherosclerosis.2020.01.004 | Citation | Wang Z, et al. (2020) Myeloid atg5 deletion impairs n-3 PUFA-mediated atheroprotection. Atherosclerosis 295:8-17 |
| abstractText | 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. |
