| First Author | Leng S | Year | 2016 |
| Journal | J Lipid Res | Volume | 57 |
| Issue | 6 | Pages | 1006-16 |
| PubMed ID | 27063951 | Mgi Jnum | J:324317 |
| Mgi Id | MGI:6869384 | Doi | 10.1194/jlr.M065888 |
| Citation | Leng S, et al. (2016) Ursolic acid enhances macrophage autophagy and attenuates atherogenesis. J Lipid Res 57(6):1006-16 |
| abstractText | Macrophage autophagy has been shown to be protective against atherosclerosis. We previously discovered that ursolic acid (UA) promoted cancer cell autophagy. In the present study, we aimed to examine whether UA enhances macrophage autophagy in the context of atherogenesis. Cell culture study showed that UA enhanced autophagy of macrophages by increasing the expression of Atg5 and Atg16l1, which led to altered macrophage function. UA reduced pro-interleukin (IL)-1beta protein levels and mature IL-1beta secretion in macrophages in response to lipopolysaccharide (LPS), without reducing IL-1beta mRNA expression. Confocal microscopy showed that in LPS-treated macrophages, UA increased LC3 protein levels and LC3 appeared to colocalize with IL-1beta. In cholesterol-loaded macrophages, UA increased cholesterol efflux to apoAI, although it did not alter mRNA or protein levels of ABCA1 and ABCG1. Electron microscopy showed that UA induced lipophagy in acetylated LDL-loaded macrophages, which may result in increased cholesterol ester hydrolysis in autophagolysosomes and presentation of free cholesterol to the cell membrane. In LDLR(-/-) mice fed a Western diet to induce atherogenesis, UA treatment significantly reduced atherosclerotic lesion size, accompanied by increased macrophage autophagy. In conclusion, the data suggest that UA promotes macrophage autophagy and, thereby, suppresses IL-1beta secretion, promotes cholesterol efflux, and attenuates atherosclerosis in mice. |
