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针对舒张功能障碍的冠心病患者进行的非靶向代谢组学分析显示氧化途径紊乱。

Untargeted metabolomic analysis of coronary artery disease patients with diastolic dysfunction show disturbed oxidative pathway.

机构信息

Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan.

Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.

出版信息

Metabolomics. 2019 Jun 24;15(7):98. doi: 10.1007/s11306-019-1559-5.

DOI:10.1007/s11306-019-1559-5
PMID:31236740
Abstract

INTRODUCTION

Left ventricular diastolic dysfunction (LVDD) is common in patients with coronary artery disease (CAD) with prevalence estimates of 34% and constitutes a predictor of all-cause mortality. Although diastolic dysfunction is induced by myocardial ischemia and has been shown to alter the clinical course, the role of coronary artery disease in the diastolic dysfunction and its progression into heart failure has not been completely elucidated.

OBJECTIVE

The present study was conducted to identify possible metabolites in coronary artery disease patients that are differentially regulated in patients with diastolic dysfunction.

METHODS

The serum of CAD (n = 75) patients and young healthy volunteers (n = 43) were analysed by using gas chromatography mass spectrometry (GC-MS) technique. Pre-processing of data results in 1547 features; among them 1064 features were annotated using NIST library.

RESULTS AND CONCLUSION

Fifteen metabolites were found to be statistically different between cases and control. Variation in metabolites were identified and correlated with several clinically important echocardiography parameters i.e. LVDD grades, ejection fraction (EF) and E/e' values. The results suggested that metabolic products of fatty acid oxidation and glucose oxidation pathways such as oleic acid, stearic acid, palmitic acid, linoleic acid, galactose, pyruvic and lactic acids are predominantly up regulated in patients with coronary artery disease and severity of diastolic dysfunction appears to be linked to increase in fatty acid oxidation and inflammation. The metabolic fingerprints of these patients give us an insight into the pathophysiological mechanism of diastolic dysfunction in coronary artery disease patients although it did not identify validated novel markers.

摘要

简介

左心室舒张功能障碍(LVDD)在患有冠状动脉疾病(CAD)的患者中很常见,其患病率估计为 34%,并且是全因死亡率的预测指标。尽管舒张功能障碍是由心肌缺血引起的,并已表明会改变临床病程,但 CAD 在舒张功能障碍及其进展为心力衰竭中的作用尚未完全阐明。

目的

本研究旨在确定 CAD 患者中可能存在的代谢物,这些代谢物在舒张功能障碍患者中存在差异调节。

方法

使用气相色谱-质谱联用(GC-MS)技术分析 CAD(n=75)患者和年轻健康志愿者(n=43)的血清。对数据的预处理导致出现 1547 个特征;其中 1064 个特征使用 NIST 库进行注释。

结果和结论

发现 15 种代谢物在病例和对照组之间存在统计学差异。鉴定出代谢物的变化,并与几个重要的临床超声心动图参数相关,即 LVDD 分级、射血分数(EF)和 E/e' 值。结果表明,脂肪酸氧化和葡萄糖氧化途径的代谢产物,如油酸、硬脂酸、棕榈酸、亚油酸、半乳糖、丙酮酸和乳酸,在 CAD 患者中主要上调,并且舒张功能障碍的严重程度似乎与脂肪酸氧化和炎症的增加有关。尽管这些患者的代谢指纹没有识别出经过验证的新型标志物,但它使我们深入了解 CAD 患者舒张功能障碍的病理生理机制。

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