Department of Anatomy and Cell Biology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, 409-3898, Japan.
Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, 409-3898, Japan.
Metabolomics. 2018 Feb 27;14(4):38. doi: 10.1007/s11306-018-1334-z.
Atherosclerotic diseases are the leading cause of death worldwide. Biomarkers of atherosclerosis are required to monitor and prevent disease progression. While mass spectrometry is a promising technique to search for such biomarkers, its clinical application is hampered by the laborious processes for sample preparation and analysis.
We developed a rapid method to detect plasma metabolites by probe electrospray ionization mass spectrometry (PESI-MS), which employs an ambient ionization technique enabling atmospheric pressure rapid mass spectrometry. To create an automatic diagnosis system of atherosclerotic disorders, we applied machine learning techniques to the obtained spectra.
Using our system, we successfully discriminated between rabbits with and without dyslipidemia. The causes of dyslipidemia (genetic lipoprotein receptor deficiency or dietary cholesterol overload) were also distinguishable by this method. Furthermore, after induction of atherosclerosis in rabbits with a cholesterol-rich diet, we were able to detect dynamic changes in plasma metabolites. The major metabolites detected by PESI-MS included cholesterol sulfate and a phospholipid (PE18:0/20:4), which are promising new biomarkers of atherosclerosis.
We developed a remarkably fast and easy method to detect potential new biomarkers of atherosclerosis in plasma using PESI-MS.
动脉粥样硬化疾病是全球范围内导致死亡的主要原因。需要使用动脉粥样硬化生物标志物来监测和预防疾病进展。虽然质谱分析是一种很有前途的寻找此类生物标志物的技术,但由于样品制备和分析过程繁琐,其临床应用受到了阻碍。
我们开发了一种通过探针电喷雾电离质谱(PESI-MS)快速检测血浆代谢物的方法,该方法采用了一种能够在大气压下进行快速质谱分析的环境电离技术。为了创建动脉粥样硬化疾病的自动诊断系统,我们将机器学习技术应用于获得的光谱。
使用我们的系统,我们成功地区分了有和没有血脂异常的兔子。这种方法还可以区分血脂异常的原因(脂蛋白受体基因缺陷或饮食胆固醇过载)。此外,在用富含胆固醇的饮食诱导兔子发生动脉粥样硬化后,我们能够检测到血浆代谢物的动态变化。通过 PESI-MS 检测到的主要代谢物包括胆固醇硫酸酯和一种磷脂(PE18:0/20:4),它们是动脉粥样硬化的有前途的新生物标志物。
我们开发了一种使用 PESI-MS 快速、简便地检测血浆中潜在动脉粥样硬化新生物标志物的方法。