Plasma acylcarnitines are associated with pulmonary hypertension.
Plasma acylcarnitines are associated with pulmonary hypertension.
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DOI：
10.1086/690554
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发表时间：
2017-03
影响因子：
2.6
通讯作者：
Rajagopal S
中科院分区：
文献类型：
--
作者：
Luo N;Craig D;Ilkayeva O;Muehlbauer M;Kraus WE;Newgard CB;Shah SH;Rajagopal S
通过血浆代谢组学量化肺动脉高压（PH）的代谢紊乱可以识别有助于诊断和治疗的生物标志物。本文的目的是检验以下假设：与对照组相比，PH 患者中以及与左心疾病相关的 PH 的不同血流动力学亚型之间，循环代谢物的表达存在差异。我们研究了参加 CATHGEN 生物样本库的 PH 患者（右心导管检查 mPAP ≥ 25 mmHg；n = 280）。其中，133 例符合毛细血管后 PH 标准，82 例符合毛细血管前和毛细血管后 PH 组合 (CpcPH) 标准，65 例符合毛细血管前 PH 标准。使用串联流动注射质谱法对 63 种代谢物（酰基肉碱、氨基酸和酮）进行了靶向分析。使用多变量线性回归来确定 PH 病例、PH 亚型和非 PH 对照之间主成分分析得出的代谢因子的差异。在调整后的模型中，所有 PH 病例中加载长链酰基肉碱的代谢因子均高于非 PH 对照 (P = 0.00008)，但在 CpcPH 和毛细血管后 PH 之间没有差异 (P = 0.56)。在亚型分析中，与对照组相比（分别为 P = 0.002 和 P = 0.01）以及与毛细血管后 PH 相比（分别为 P = 0.04 和 P = 0.02），CpcPH 患者的尿素循环氨基酸和短链酰基肉碱负载因子水平较低。与对照组相比，PH 值与更高浓度的长链酰基肉碱密切相关。毛细血管后 PH 和 CpcPH 与不同的代谢组学特征微弱相关。这些发现表明 PH 亚型中存在独特的代谢异常，并可能反映潜在的病理生理学。
Quantifying metabolic derangements in pulmonary hypertension (PH) by plasma metabolomics could identify biomarkers useful for diagnosis and treatment. The objective of this paper is to test the hypotheses that circulating metabolites are differentially expressed in PH patients compared with controls and among different hemodynamic subtypes of PH associated with left heart disease. We studied patients enrolled in the CATHGEN biorepository with PH (right heart catheterization mPAP ≥ 25 mmHg; n = 280). Of these, 133 met criteria for postcapillary PH, 82 for combined precapillary and postcapillary PH (CpcPH), and 65 for precapillary PH. Targeted profiling of 63 metabolites (acylcarnitines, amino acids, and ketones) was performed using tandem flow injection mass spectrometry. Multivariable linear regression was used to determine differences in metabolite factors derived from a principal components analysis between PH cases, PH subtypes, and non-PH controls. In adjusted models, the metabolite factor loaded with long-chain acylcarnitines was higher in all PH cases versus non-PH controls (P = 0.00008), but did not discriminate between CpcPH and postcapillary PH (P = 0.56). In analyses of subtypes, CpcPH patients had lower levels of factors loaded with urea cycle amino acids and short chain acylcarnitines as compared to controls (P = 0.002 and P = 0.01, respectively) and as compared to postcapillary PH (P = 0.04 and P = 0.02, respectively). Compared to controls, PH was strongly associated with greater concentrations of long-chain acylcarnitines. Postcapillary PH and CpcPH were weakly associated with distinct metabolomic profiles. These findings suggest the presence of unique metabolic abnormalities in subtypes of PH and may reflect underlying pathophysiology.