Myeloid atg5 deletion impairs n-3 PUFA-mediated atheroprotection
| Autor: | Manal Zabalawi, Russel C. Sequeira, Yan Nie, Xuewei Zhu, Elena Boudyguina, Tiantong Ou, Jennifer H. Madenspacher, Qingxia Zhao, Zhan Wang, Jonathan M. Nelson, Michael B. Fessler |
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| Rok vydání: | 2020 |
| Předmět: |
Male
medicine.medical_specialty Saturated fat ATG5 Inflammation Article Autophagy-Related Protein 5 Mice chemistry.chemical_compound Internal medicine Fatty Acids Omega-3 medicine Animals Efferocytosis Mice Knockout chemistry.chemical_classification Triglyceride Cholesterol Atherosclerosis Fish oil Lipids Disease Models Animal Endocrinology Receptors LDL chemistry Female lipids (amino acids peptides and proteins) medicine.symptom Cardiology and Cardiovascular Medicine Polyunsaturated fatty acid |
| Zdroj: | Atherosclerosis |
| ISSN: | 0021-9150 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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