吲哚胺2,3-双加氧酶依赖性色氨酸代谢产物和内脂素作为妊娠合并肺动脉高压的有效诊断生物标志物
IDO-Dependent Tryptophan Metabolites and Endocan as Effective Diagnostic Biomarkers for Pregnancy with Pulmonary Hypertension.
作者信息
Peng Guixin, Liu Zhuanghua, Wang Wenli
机构信息
Department of Critical Care Medicine, Changzhou Maternal and Child Health Hospital, Changzhou Medical Center of Nanjing Medical University, Changzhou, People's Republic of China.
Department of Obstetrics, Changzhou Maternal and Child Health Hospital, Changzhou Medical Center of Nanjing Medical University, Changzhou, People's Republic of China.
出版信息
Int J Womens Health. 2025 Jul 19;17:2205-2216. doi: 10.2147/IJWH.S527345. eCollection 2025.
OBJECTIVE
Pregnancy with pulmonary hypertension (PPH) is one of the main causes of maternal heart failure and death. Endocan is a well-established soluble proteoglycan biomarker for endothelial dysfunction and inflammation. The Indoleamine 2, 3 dioxygenase (IDO) enzyme family comprises IDO1, IDO2, and TDO2, with IDO1-dependent tryptophan metabolites being particularly promising as candidate biomarkers for pulmonary hypertension (PH). However, there have been no reports on the relationship between endocan and IDO1-dependent metabolite and the progression of PPH. The study enrolled 62 patients with PPH and 86 age- and sex-matched healthy people. The concentrations of endocan, B-type natriuretic peptide (BNP), and N-terminal prohormone of BNP (NT-pro BNP) in the serum were detected by enzyme-linked immunosorbent assay.
METHODS
The Pearson correlation coefficient analyzed the correlation between endocan level and BNP and NT-pro BNP. The concentrations of IDO-dependent tryptophan metabolites in the serum were measured by high-performance liquid chromatography-tandem mass spectrometry. The diagnostic value of endocan and IDO-dependent tryptophan metabolites for PPH was evaluated by the receiver operating characteristic curve (ROC).
RESULTS
Results suggested that endocan (PPH vs control: 30.56±3.61 vs 24.53±3.00 ng/mL), BNP (243.40,63.03 vs 98.60,93.35 pg/mL), NT pro-BNP (654.65,363.80 vs 141.70,158.55 pg/mL), kynurenine (1.80±0.23 vs 1.53±0.28 AU), kynurenate (5.17±0.24 vs 4.91±0.27 AU), anthranilate (5.15,2.13 vs 3.00,1.33 AU), and quinolinate (3.62±0.80 vs 2.77±0.81 AU) (all p<0.001) were upregulated in PPH patients. Moreover, Endocan levels showed strong positive correlations with both BNP (r=0.590, p<0.001) and NT pro-BNP (r=0.801, p<0.001). ROC curve showed that the combination of endocan and IDO-dependent tryptophan metabolites had diagnostic value to PPH (AUC: 0.935; 95% CI: 0.896-0.974).
CONCLUSION
In short, we demonstrated that IDO-dependent tryptophan metabolites and endocan could be used as diagnostic biomarkers of PPH.
目的
妊娠合并肺动脉高压（PPH）是孕产妇心力衰竭和死亡的主要原因之一。内脂素是一种公认的用于评估内皮功能障碍和炎症的可溶性蛋白聚糖生物标志物。吲哚胺2,3-双加氧酶（IDO）酶家族包括IDO1、IDO2和TDO2，其中IDO1依赖性色氨酸代谢产物作为肺动脉高压（PH）的候选生物标志物尤其具有前景。然而，关于内脂素与IDO1依赖性代谢产物之间的关系以及PPH的进展尚无报道。本研究纳入了62例PPH患者和86例年龄及性别匹配的健康人。采用酶联免疫吸附测定法检测血清中内脂素、B型利钠肽（BNP）和N末端B型利钠肽原（NT-pro BNP）的浓度。
方法
采用Pearson相关系数分析内脂素水平与BNP和NT-pro BNP之间的相关性。采用高效液相色谱-串联质谱法测定血清中IDO依赖性色氨酸代谢产物的浓度。通过受试者工作特征曲线（ROC）评估内脂素和IDO依赖性色氨酸代谢产物对PPH的诊断价值。
结果
结果表明，PPH患者的内脂素（PPH组与对照组：30.56±3.61 vs 24.53±3.00 ng/mL）、BNP（243.40,63.03 vs 98.60,93.35 pg/mL）、NT-pro BNP（654.65,363.80 vs 141.70,158.55 pg/mL）、犬尿氨酸（1.80±0.23 vs 1.53±0.28 AU）、犬尿酸（5.17±0.24 vs 4.91±0.27 AU）、邻氨基苯甲酸（5.15,2.13 vs 3.00,1.33 AU）和喹啉酸（3.62±0.80 vs 2.77±0.81 AU）均上调（所有p<0.001）。此外，内脂素水平与BNP（r=0.590，p<0.001）和NT-pro BNP（r=0.801，p<0.001）均呈强正相关。ROC曲线显示，内脂素与IDO依赖性色氨酸代谢产物联合对PPH具有诊断价值（AUC：0.935；95%CI：0.896-0.974）。
结论
简而言之，我们证明了IDO依赖性色氨酸代谢产物和内脂素可作为PPH的诊断生物标志物。
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