A host lipase prevents lipopolysaccharide-induced foam cell formation.
A host lipase prevents lipopolysaccharide-induced foam cell formation.
复制标题
宿主脂肪酶可防止脂多糖诱导的泡沫细胞形成
DOI：
10.1016/j.isci.2021.103004
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发表时间：
2021-09-24
期刊：
影响因子：
5.8
通讯作者：
Lu M
中科院分区：
文献类型：
--
作者：
Feng J;Jiang W;Cheng X;Zou B;Varley AW;Liu T;Qian G;Zeng W;Tang J;Zhao Q;Chu Y;Wei Y;Li X;Munford RS;Lu M
虽然微生物相关分子模式（MAMP）分子可以促进胆固醇在巨噬细胞中的积累，但尚未描述宿主来源的MAMP失活机制的存在，该机制可以防止泡沫细胞形成。在这里，我们测试了酰氧酰基水解酶（AOAH）的能力，宿主脂肪酶，灭活革兰氏阴性细菌脂多糖（LPS），以防止小鼠泡沫细胞形成。在暴露于小剂量腹腔内LPS后，Aoah−/−巨噬细胞产生更多的低密度脂蛋白受体和更少的载脂蛋白E，并比Aoah+/+巨噬细胞积累更多的胆固醇。Aoah−/−巨噬细胞还保持了几种促炎特征。使用血管周围项圈放置模型，我们发现Aoah−/−小鼠在喂食高脂肪，高胆固醇饮食并接受小剂量LPS后，比Aoah+/+小鼠产生更多的颈动脉泡沫细胞。这是第一次证明在体内使刺激性MAMP失活的酶可以减少动脉巨噬细胞中的胆固醇积累和炎症。酰氧酰基水解酶防止脂多糖诱导的巨噬细胞胆固醇积聚AOAH还防止脂多糖暴露后的长期炎症AOAH增强脂多糖暴露的巨噬细胞线粒体功能AOAH改善脂多糖诱导的颈动脉病变中泡沫细胞积聚脂质;分子生物学;细胞生物学
Although microbe-associated molecular pattern (MAMP) molecules can promote cholesterol accumulation in macrophages, the existence of a host-derived MAMP inactivation mechanism that prevents foam cell formation has not been described. Here, we tested the ability of acyloxyacyl hydrolase (AOAH), the host lipase that inactivates gram-negative bacterial lipopolysaccharides (LPSs), to prevent foam cell formation in mice. Following exposure to small intraperitoneal dose(s) of LPSs, Aoah−/− macrophages produced more low-density lipoprotein receptor and less apolipoprotein E and accumulated more cholesterol than did Aoah+/+ macrophages. The Aoah−/− macrophages also maintained several pro-inflammatory features. Using a perivascular collar placement model, we found that Aoah−/− mice developed more carotid artery foam cells than did Aoah+/+ mice after they had been fed a high fat, high cholesterol diet, and received small doses of LPSs. This is the first demonstration that an enzyme that inactivates a stimulatory MAMP in vivo can reduce cholesterol accumulation and inflammation in arterial macrophages. Acyloxyacyl hydrolase prevents LPS-induced cholesterol accumulation in macrophages AOAH also prevents prolonged inflammation after LPS exposure AOAH enhances mitochondrial function in LPS-exposed macrophages AOAH ameliorates LPS-induced foam cell accumulation in carotid arterial lesions Lipid; Molecular biology; Cell biology
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影响因子：
37.8
作者：
Malik TH;Cortini A;Carassiti D;Boyle JJ;Haskard DO;Botto M
通讯作者：
Botto M
影响因子：
30.5
作者：
通讯作者：
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巨噬细胞线粒体能量状态调节胆固醇外排，并在动脉粥样硬化中通过抗MIR33增强。
影响因子：
20.1
作者：
Karunakaran D;Thrush AB;Nguyen MA;Richards L;Geoffrion M;Singaravelu R;Ramphos E;Shangari P;Ouimet M;Pezacki JP;Moore KJ;Perisic L;Maegdefessel L;Hedin U;Harper ME;Rayner KJ
通讯作者：
Rayner KJ
影响因子：
10.8
作者：
Gitlin, Jonathan M.;Loftin, Charles D.
通讯作者：
Loftin, Charles D.
DOI：
10.1038/nri3520
发表时间：
2013-10
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
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