, 14:38 | Cite as

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

  • Hisashi Johno
  • Kentaro YoshimuraEmail author
  • Yuki Mori
  • Tokuhide Kimura
  • Manabu Niimi
  • Masaki Yamada
  • Tetsuo Tanigawa
  • Jianglin Fan
  • Sen TakedaEmail author
Original Article



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.


Probe electrospray ionization mass spectrometry Atherosclerosis Dyslipidemia Blood plasma Machine learning 



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, [].

Compliance with ethical standards

Conflict of interest

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.

Supplementary material

11306_2018_1334_MOESM1_ESM.pdf (8.9 mb)
Supplementary material 1 (PDF 9063 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Hisashi Johno
    • 1
  • Kentaro Yoshimura
    • 1
    Email author
  • Yuki Mori
    • 1
  • Tokuhide Kimura
    • 2
  • Manabu Niimi
    • 2
  • Masaki Yamada
    • 3
  • Tetsuo Tanigawa
    • 3
  • Jianglin Fan
    • 2
  • Sen Takeda
    • 1
    Email author
  1. 1.Department of Anatomy and Cell Biology, Interdisciplinary Graduate School of MedicineUniversity of YamanashiChuoJapan
  2. 2.Department of Molecular Pathology, Interdisciplinary Graduate School of MedicineUniversity of YamanashiChuoJapan
  3. 3.Analytical and Measuring Instruments Division, Global Application Development CenterShimadzu CorporationKyotoJapan

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