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High-resolution metabolomics study revealing l-homocysteine sulfinic acid, cysteic acid, and carnitine as novel biomarkers for high acute myocardial infarction risk.
Metabolism ( IF 9.8 ) Pub Date : 2019-12-24 , DOI: 10.1016/j.metabol.2019.154051
Adnan Khan 1 , Yoonjeong Choi 2 , Joung Hwan Back 3 , Sunmi Lee 3 , Sun Ha Jee 2 , Youngja H Park 1
Affiliation  

BACKGROUND Identifying changes in serum metabolites before the occurrence of acute myocardial infarction (AMI) is an important approach for finding novel biomarkers of AMI. METHODS In this prospective cohort study, serum samples obtained from patients at risk of AMI (n = 112) and non-risk controls (n = 89) were tested using high-resolution metabolomics (HRM). Partial least-squares discriminant analysis (PLS-DA), along with univariate analysis using a false discovery rate (FDR) of q = 0.05 were performed to discriminate metabolic profiles and to determine significantly different metabolites between healthy control and AMI risk groups. RESULTS PLS-DA significantly separated the AMI risk sera from control sera. The metabolites associated with amino acid biosynthesis, 2-oxocarboxylic acid, tryptophan, and amino sugar and nucleotide sugar metabolism pathways were mainly elevated in patients at risk of AMI. Further validation and quantification by MS/MS showed that tryptophan, carnitine, L-homocysteine sulfinic acid (L-HCSA), and cysteic acid (CA) were upregulated, while L-cysteine and L-cysteine sulfinic acid (L-CSA) were downregulated, specifically among AMI risk sera. Additionally, these discriminant metabolic profiles were not related to hypertension, smoking or alcoholism. CONCLUSION In conclusion, detecting upregulated L-HCSA and CA along with carnitine among patients at risk for AMI could serve as promising non-invasive biomarkers for early AMI detection.

中文翻译:

高分辨率代谢组学研究揭示了L-高半胱氨酸亚磺酸,半胱氨酸和肉碱是高度急性心肌梗死风险的新型生物标志物。

背景技术在急性心肌梗塞(AMI)发生之前识别血清代谢物的变化是寻找AMI的新生物标志物的重要方法。方法在这项前瞻性队列研究中,使用高分辨率代谢组学(HRM)对从有AMI风险(n = 112)和无风险对照组(n = 89)的患者获得的血清样本进行了测试。进行了偏最小二乘判别分析(PLS-DA)以及使用q = 0.05的错误发现率(FDR)进行的单变量分析,以区分代谢谱并确定健康对照组和AMI风险组之间的代谢物显着不同。结果PLS-DA可将AMI风险血清与对照血清显着分离。与氨基酸生物合成有关的代谢物,2-氧代羧酸,色氨酸,氨基糖和核苷酸糖代谢途径主要在有AMI风险的患者中升高。通过MS / MS进行的进一步验证和定量分析表明,色氨酸,肉碱,L-高半胱氨酸亚磺酸(L-HCSA)和半胱氨酸(CA)被上调,而L-半胱氨酸和L-半胱氨酸亚磺酸(L-CSA)被上调。下调,特别是在AMI风险血清中。另外,这些判别性代谢特征与高血压,吸烟或酒精中毒无关。结论总之,在有AMI风险的患者中检测L-HCSA和CA以及肉碱的表达上调可以作为早期AMI检测的有前途的非侵入性生物标记。和半胱氨酸(CA)被上调,而L-半胱氨酸和L-半胱氨酸亚磺酸(L-CSA)被下调,特别是在AMI风险血清中。另外,这些判别性代谢特征与高血压,吸烟或酒精中毒无关。结论总之,在有AMI风险的患者中检测L-HCSA和CA以及肉碱的表达上调可以作为早期AMI检测的有前途的非侵入性生物标记。和半胱氨酸(CA)被上调,而L-半胱氨酸和L-半胱氨酸亚磺酸(L-CSA)被下调,特别是在AMI风险血清中。另外,这些判别性代谢特征与高血压,吸烟或酒精中毒无关。结论总之,在有AMI风险的患者中检测L-HCSA和CA以及肉碱的表达上调可以作为早期AMI检测的有前途的非侵入性生物标记。
更新日期:2019-12-25
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