Metabolomics reveals metabolite changes of patients with pulmonary arterial hypertension in China
Metabolomics reveals metabolite changes of patients with pulmonary arterial hypertension in China
复制标题
代谢组学揭示中国肺动脉高压患者的代谢变化
DOI：
10.1111/jcmm.14937
复制
发表时间：
2020-01-16
影响因子：
5.3
通讯作者：
Zhou, Shenhua
中科院分区：
文献类型：
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作者：
Chen, Chenyang;Luo, Fei;Zhou, Shenhua
肺动脉高压（PAH）的具体机制尚不清楚。本研究旨在利用代谢组学方法，通过鉴定新的多环芳烃生物标志物，探索多环芳烃的潜在机制。本文收集了40例特发性PAH （IPAH）患者、20例先天性心脏病相关性PAH （CHD - PAH）患者和20例健康对照者的血清样本，并采用超高效液相色谱-高分辨率质谱（UPLC - HRMS）对其进行了分析。应用正交偏最小二乘判别分析（OPLS - DA）筛选潜在的生物标志物。这些结果在MCT诱导的PAH大鼠模型中得到了验证。OPLS‐DA模型成功地筛选了不同的代谢物特征，分别将IPAH和CHD‐PAH患者与健康对照组区分开来（26种代谢物和15种代谢物）。来自OPLS‐DA的无偏分析鉴定出来自PAH患者的31种代谢物与健康对照相比有差异调节。我们的分析显示，与健康人相比，PAH患者的不同代谢途径，包括脂质代谢、葡萄糖代谢、氨基酸代谢和磷脂代谢途径失调。在这些代谢途径失调的代谢物中，脂质代谢和脂肪酸氧化的代谢物（溶血磷脂酰胆碱、磷脂酰胆碱、苏酸、棕榈油酸、N -乙酰胆碱- d -鞘磷脂、油酸、棕榈酸和2 -辛酰肉碱代谢物）被发现与多环芳烃密切相关。实时定量PCR和Western blot分析结果显示，MCT组右心/肺组织中LDHA、CD36、FASN、PDK1、GLUT1和CPT‐1的表达明显高于对照组。
The specific mechanism of pulmonary arterial hypertension (PAH) remains elusive. The present study aimed to explore the underlying mechanism of PAH through the identity of novel biomarkers for PAH using metabolomics approach. Serum samples from 40 patients with idiopathic PAH (IPAH), 20 patients with congenital heart disease‐associated PAH (CHD‐PAH) and 20 healthy controls were collected and analysed by ultra‐high‐performance liquid chromatography coupled with high‐resolution mass spectrometry (UPLC‐HRMS). Orthogonal partial least square‐discriminate analysis (OPLS‐DA) was applied to screen potential biomarkers. These results were validated in monocrotaline (MCT)‐induced PAH rat model. The OPLS‐DA model was successful in screening distinct metabolite signatures which distinguished IPAH and CHD‐PAH patients from healthy controls, respectively (26 and 15 metabolites). Unbiased analysis from OPLS‐DA identified 31 metabolites from PAH patients which were differentially regulated compared to the healthy controls. Our analysis showed dysregulation of the different metabolic pathways, including lipid metabolism, glucose metabolism, amino acid metabolism and phospholipid metabolism pathways in PAH patients compared to their healthy counterpart. Among these metabolites from dysregulated metabolic pathways, a panel of metabolites from lipid metabolism and fatty acid oxidation (lysophosphatidylcholine, phosphatidylcholine, perillic acid, palmitoleic acid, N‐acetylcholine‐d‐sphingomyelin, oleic acid, palmitic acid and 2‐Octenoylcarnitine metabolites) were found to have a close association with PAH. The results from the analysis of both real‐time quantitative PCR and Western blot showed that expression of LDHA, CD36, FASN, PDK1 GLUT1 and CPT‐1 in right heart/lung were significantly up‐regulated in MCT group than the control group.