Macrophage Lysophosphatidylcholine Acyltransferase 3 Deficiency-Mediated Inflammation Is Not Sufficient to Induce Atherosclerosis in a Mouse Model
| Autor: | Hui Jiang, Zhiqiang Li, Chongmin Huan, Xian-Cheng Jiang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | Frontiers in Cardiovascular Medicine, Vol 5 (2019) |
| Druh dokumentu: | article |
| ISSN: | 2297-055X 27342018 |
| DOI: | 10.3389/fcvm.2018.00192 |
| Popis: | Mammalian cell membrane phosphatidylcholines (PCs), the major phospholipids, exhibit diversity which is controlled by Lands' cycle or PC remodeling pathway. Lysophosphatidylcholine acyltransferase (LPCAT) is one of the major players in the pathway and plays an important role in maintaining cell membrane structure and function. LPCAT3 is highly expressed in macrophages, however, its role in mediating inflammation is still not understood, since contradictory results were reported previously. The order of LPCAT mRNA levels in mouse macrophages is as follows: LPCAT3 > LPCAT1 > LPCAT2 >> LPCAT4. In order to investigate the role of LPCAT3 in macrophages, we prepared myeloid cell-specific Lpcat3 knockout (KO) mice and found that the deficiency significantly reduced certain polyunsaturated phosphatidylcholines, such as 16:0/20:4, 18:1/18:2, 18:0/20:4, and 18:1/20:4 in macrophage plasma membrane. Lpcat3 deficiency significantly increased toll like receptor 4 protein and phosphorylated c-Src in membrane lipid rafts, and increased LPS-induced IL-6 and TNFα releasing through activation of MAP kinases and NFκB. Moreover, the ablation of LPCAT3 in macrophages significantly increase of M1 macrophages. However, macrophage deletion of Lpcat3 in (LDL receptor) Ldlr KO mice, both male and female, on a Western type diet, did not have a significant impact on atherogenesis. In conclusion, LPCAT3 is one of LPCATs in macrophages, involved in PC remodeling. LPCAT3 deficiency has no effect on cholesterol efflux. However, the deficiency promotes macrophage inflammatory response, but such an effect has a marginal influence on the development of atherosclerosis. |
| Databáze: | Directory of Open Access Journals |
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