Trimethylamine-N-oxide (TMAO)-induced atherosclerosis is associated with bile acid metabolism
Trimethylamine-N-oxide (TMAO)-induced atherosclerosis is associated with bile acid metabolism
复制标题
DOI：
10.1186/s12944-018-0939-6
复制
发表时间：
2018-12-19
影响因子：
4.5
通讯作者：
Wang, Yuming
中科院分区：
文献类型：
--
作者：
Ding, Lin;Chang, Mengru;Wang, Yuming
背景近年来，血浆中氧化三甲胺（TMAO）水平被证实与动脉粥样硬化的发生发展有关。在旨在改善动脉粥样硬化病变的靶点中，诱导胆汁酸合成以清除体内多余的胆固醇是一种有效的途径。单个胆汁酸作为核受体的内源性配体对调节胆汁酸代谢具有不同的作用。目前尚不清楚胆汁酸的配置文件是否与TMAO诱导的动脉粥样硬化的发展mechanically linked.MethodsMale apoE（-/-）小鼠喂养对照饮食含有0.3%TMAO为8周。主动脉病变的发展和血脂谱进行了测定。通过液相色谱分离和质谱检测（LC-MS）测定胆汁、肝脏和血清中的胆汁酸谱。实时荧光定量PCR检测肝内胆汁酸代谢相关基因mRNA表达。
BackgroundRecently, trimethylamine-N-oxide (TMAO) plasma levels have been proved to be associated with atherosclerosis development. Among the targets aimed to ameliorating atherosclerotic lesions, inducing bile acid synthesis to eliminate excess cholesterol in body is an effective way. Individual bile acid as endogenous ligands for the nuclear receptor has differential effects on regulating bile acid metabolism. It is unclear whether bile acid profiles are mechanistically linked to TMAO-induced development of atherosclerosis.MethodsMale apoE(-/-) mice were fed with control diet containing 0.3% TMAO for 8weeks. Aortic lesion development and serum lipid profiles were determined. Bile acid profiles in bile, liver and serum were measured by liquid chromatographic separation and mass spectrometric detection (LC-MS). Real-time PCRs were performed to analyze mRNA expression of genes related to hepatic bile acid metabolism.ResultsThe total plaque areas in the aortas strongly increased 2-fold (P