ABCA1
ABCG1公司
油红O
泡沫电池
胆固醇逆向转运
载脂蛋白E
胆固醇
化学
脂质代谢
免疫印迹
p38丝裂原活化蛋白激酶
安普克
脂蛋白
磷酸化
细胞生物学
分子生物学
生物
生物化学
蛋白激酶A
脂肪组织
内科学
医学
运输机
基因
脂肪生成
疾病
作者
Jin Zou,Can Xu,Zhen-Wang Zhao,Shan-Hui Yin,Gang Wang
标识
DOI:10.1186/s12967-022-03542-0
摘要
Asprosin, a newly discovered adipokine, is a C-terminal cleavage product of profibrillin. Asprosin has been reported to participate in lipid metabolism and cardiovascular disease, but its role in atherogenesis remains elusive.Asprosin was overexpressed in THP-1 macrophage-derived foam cells and apoE-/- mice using the lentiviral vector. The expression of relevant molecules was determined by qRT-PCR and/or western blot. The intracellular lipid accumulation was evaluated by high-performance liquid chromatography and Oil red O staining. HE and Oil red O staining was employed to assess plaque burden in vivo. Reverse cholesterol transport (RCT) efficiency was measured using [3H]-labeled cholesterol.Exposure of THP-1 macrophages to oxidized low-density lipoprotein down-regulated asprosin expression. Lentivirus-mediated overexpression of asprosin promoted cholesterol efflux and inhibited lipid accumulation in THP-1 macrophage-derived foam cells. Mechanistic analysis revealed that asprosin overexpression activated p38 and stimulated the phosphorylation of ETS-like transcription factor (Elk-1) at Ser383, leading to Elk-1 nuclear translocation and the transcriptional activation of ATP binding cassette transporters A1 (ABCA1) and ABCG1. Injection of lentiviral vector expressing asprosin diminished atherosclerotic lesion area, increased plaque stability, improved plasma lipid profiles and facilitated RCT in apoE-/- mice. Asprosin overexpression also increased the phosphorylation of p38 and Elk-1 as well as up-regulated the expression of ABCA1 and ABCG1 in the aortas.Asprosin inhibits lipid accumulation in macrophages and decreases atherosclerotic burden in apoE-/- mice by up-regulating ABCA1 and ABCG1 expression via activation of the p38/Elk-1 signaling pathway.
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