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Detection of potential new biomarkers of atherosclerosis by probe electrospray ionization mass spectrometry

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Abstract

Introduction

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.

Methods

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.

Results

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.

Conclusion

We developed a remarkably fast and easy method to detect potential new biomarkers of atherosclerosis in plasma using PESI-MS.

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Acknowledgements

We thank Ayumi Iizuka for technical assistance with the PESI-MS analyses. This work was partially supported by JSPS KAKENHI Grant Number 16K08964 (Grant-in-Aid for Scientific Research (C) to K. Y.).

Availability of data

The datasets generated during and/or analyzed during the current study are available in the Figshare repository, [https://doi.org/10.6084/m9.figshare.5783205].

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, 409-3898, Japan

    Hisashi Johno, Kentaro Yoshimura, Yuki Mori & Sen Takeda

  2. Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, 409-3898, Japan

    Tokuhide Kimura, Manabu Niimi & Jianglin Fan

  3. Analytical and Measuring Instruments Division, Global Application Development Center, Shimadzu Corporation, Kyoto, 604-8511, Japan

    Masaki Yamada & Tetsuo Tanigawa

Authors
  1. Hisashi Johno
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  2. Kentaro Yoshimura
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  3. Yuki Mori
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  4. Tokuhide Kimura
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  5. Manabu Niimi
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  7. Tetsuo Tanigawa
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  8. Jianglin Fan
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  9. Sen Takeda
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Corresponding authors

Correspondence to Kentaro Yoshimura or Sen Takeda.

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The authors declare no conflict of interest.

Ethical approval

Animal experiments were performed with the approval of the Animal Care Committee of the University of Yamanashi and complied with the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health.

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Johno, H., Yoshimura, K., Mori, Y. et al. Detection of potential new biomarkers of atherosclerosis by probe electrospray ionization mass spectrometry. Metabolomics 14, 38 (2018). https://doi.org/10.1007/s11306-018-1334-z

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