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基于代谢组学的不稳定型心绞痛及其并发症潜在血浆生物标志物和代谢功能障碍的鉴定。

Identification of potential plasma biomarkers and metabolic dysfunction for unstable angina pectoris and its complication based on global metabolomics.

机构信息

Beijing University of Chinese Medicine, Beijing 100029, China.

School of Life Sciences, Beijing University of Chinese Medicine, Beijing 100029, China.

出版信息

Biosci Rep. 2019 Mar 22;39(3). doi: 10.1042/BSR20181658. Print 2019 Mar 29.

Abstract

Unstable angina pectoris (UA) is one of the most dangerous clinical symptoms of acute coronary syndrome due to the risk of myocardial ischemia, which can lead to high morbidity and mortality worldwide. Though there are many advantages in understanding the pathophysiology of UA, the identification of biomarkers for the diagnosis, prognosis, and treatment of UA remains a challenge in the clinic. A global metabolomics research based on ultra-performance liquid chromatography (UPLC) combined with Q-TOF/MS was performed to discover the metabolic profile of health controls, UA patients, and UA patients with diabetes mellitus (DM), and screen for potential biomarkers. Twenty-seven potential biomarkers were determined using pattern recognition. These biomarkers, which include free fatty acids, amino acids, lysoPE and lysoPC species, and organic acids, can benefit the clinical diagnosis of UA. Pathway analysis indicated that arginine and proline metabolism, glycerophospholipid metabolism, and purine metabolism were affected in the UA patients, uniquely. Additionally, alterations in the metabolic signatures between UA and UA-complicated DM were also explored. As a result, six differential metabolites with an area under the curve (AUC) of more than 0.85 were identified as biomarkers for the diagnosis of UA and UA complicated with DM. Pathway analysis implied tryptophan metabolism was a key metabolic pathway in UA patients with DM, which provides new insights into the pathological study and drug discovery of UA.

摘要

不稳定性心绞痛(UA)是急性冠状动脉综合征中最危险的临床症状之一,由于存在心肌缺血的风险,其在全球范围内具有较高的发病率和死亡率。虽然了解 UA 的病理生理学有很多优势,但用于诊断、预后和治疗 UA 的生物标志物的识别仍然是临床中的一个挑战。本研究采用基于超高效液相色谱(UPLC)结合 Q-TOF/MS 的全球代谢组学研究,发现健康对照者、UA 患者和合并糖尿病(DM)的 UA 患者的代谢特征,并筛选潜在的生物标志物。通过模式识别确定了 27 个潜在的生物标志物。这些生物标志物包括游离脂肪酸、氨基酸、溶血磷脂酰乙醇胺和溶血磷脂酰胆碱以及有机酸,可有益于 UA 的临床诊断。通路分析表明,精氨酸和脯氨酸代谢、甘油磷脂代谢和嘌呤代谢在 UA 患者中受到影响。此外,还探讨了 UA 与合并 DM 的 UA 之间代谢特征的变化。结果,确定了 6 个 AUC 大于 0.85 的差异代谢物作为 UA 和合并 DM 的诊断标志物。通路分析表明,色氨酸代谢是合并 DM 的 UA 患者的关键代谢通路,为 UA 的病理研究和药物发现提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0730/6430740/a314e27ac569/bsr-39-bsr20181658-g1.jpg

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