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Licensed Unlicensed Requires Authentication Published by De Gruyter October 19, 2021

Exploration of novel biomarkers for hypertensive disorders of pregnancy by comprehensive analysis of peptide fragments in blood: their potential and technologies supporting quantification

Yoshihiko Araki ORCID logo, Yoshiki Miura and Hiroshi Fujiwara


Among the many complications associated with pregnancy, hypertensive disorders of pregnancy (HDP) constitute one of the most important. Since the pathophysiology of HDP is complex, new disease biomarkers (DBMs) are needed to serve as indicators of disease activity. However, in the current status of laboratory medicine, despite the fact that blood pressure measurement has been used for a long time, not many DBMs contribute adequately to the subsequent diagnosis and treatment. In this article, we discuss studies focusing on peptide fragments in blood identified by comprehensive quantitative methods, among the currently proposed DBM candidates. Furthermore, we describe the basic techniques of peptidomics, especially quantitative proteomics, and outline the current status and challenges of measuring peptides in blood as DBM for HDP.

Corresponding author: Yoshihiko Araki, MD DMedSci, Institute for Environmental & Gender-Specific Medicine, Juntendo University Graduate School of Medicine, Chiba, Japan; Department of Obstetrics & Gynecology, Juntendo University Graduate School of Medicine, Tokyo, Japan; and Department of Pathology and Microbiology, Division of Microbiology and Immunology, Nihon University School of Medicine, Tokyo, Japan, E-mail:

Funding source: The Japan Society for the Promotion of Science

Award Identifier / Grant number: 25462575/16K11111/17K19734/17K19719/19K22681/18KK0256

Funding source: Japan Science and Technology Agency

Award Identifier / Grant number: AS2311641F/19-191030923

Funding source: The Ministry of Education, Culture, Sports, Science and Technology, Japan

Award Identifier / Grant number: “High-Tech Research Center” Project for Private Universities: matching fund subsidy

Funding source: The Japan Agency for Medical Research and Development

Award Identifier / Grant number: 17gk0110024h0001/17cm0106XXXh0001


We would like to thank all collaborators who contributed to the MS analysis and related studies.

  1. Research funding: This work was supported in part by Grants-in Aid for Scientific Research Nos. 25462575/16K11111, for Challenging Research Nos. 17K19734/17K19719/19K22681, and for Fostering Joint International Research No. 18KK0256 from the Japan Society for the Promotion of Science (JSPS), grants Nos. 17gk0110024h0001/17cm0106XXXh0001 from the Japan Agency for Medical Research and Development (AMED), grants No. AS2311641F/19-191030923 from Japan Science and Technology Agency, and “High-Tech Research Center” Project for Private Universities: matching fund subsidy from the Ministry of Education, Culture, Sports, Science and Technology, Japan.

  2. Author contributions: Y.A., Y.M., and H.F. conceived, designed, and directed the study, provided financial supports, and wrote the article. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Not applicable.

  5. Ethical approval: Not applicable.


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Received: 2021-06-18
Accepted: 2021-09-29
Published Online: 2021-10-19
Published in Print: 2022-01-26

© 2021 Walter de Gruyter GmbH, Berlin/Boston

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