Soluble amyloid precursor protein 770 is released from inflamed endothelial cells and activated platelets: A novel biomarker for acute coronary syndrome

Shinobu Kitazume, Akiomi Yoshihisa, Takayoshi Yamaki, Masayoshi Oikawa, Yuriko Tachida, Kazuko Ogawa, Rie Imamaki, Yoshiaki Hagiwara, Noriaki Kinoshita, Yasuchika Takeishi, Katsutoshi Furukawa, Naoki Tomita, Hiroyuki Arai, Nobuhisa Iwata, Takaomi Saido, Naomasa Yamamoto, Naoyuki Taniguchi

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Most Alzheimer disease (AD) patients show deposition of amyloid β (Aβ) peptide in blood vessels as well as the brain parenchyma. We previously found that vascular endothelial cells express amyloid β precursor protein (APP) 770, a different APP isoform from neuronal APP695, and produce Aβ. Since the soluble APP cleavage product, sAPP, is considered to be a possible marker for AD diagnosis, sAPP has been widely measured as a mixture of these variants. We hypothesized that measurement of the endothelial APP770 cleavage product in patients separately from that of neuronal APP695 would enable discrimination between endothelial and neurological dysfunctions. Using our newly developed ELISA system for sAPP770, we observed that inflammatory cytokines significantly enhanced sAPP770 secretion by endothelial cells. Furthermore, we unexpectedly found that sAPP770 was rapidly released from activated platelets. We also found that cerebrospinal fluid mainly contained sAPP695, while serum mostly contained sAPP770. Finally, to test our hypothesis that sAPP770 could be an indicator for endothelial dysfunction, we applied our APP770 ELISA to patients with acute coronary syndrome (ACS), in which endothelial injury and platelet activation lead to fibrous plaque disruption and thrombus formation. Development of a biomarker is essential to facilitate ACS diagnosis in clinical practice. The results revealed that ACS patients had significantly higher plasma sAPP770 levels. Furthermore, in myocardial infarction model rats, an increase in plasma sAPP preceded the release of cardiac enzymes, currently used markers for acute myocardial infarction. These findings raise the possibility that sAPP770 can be a useful biomarker for ACS.

Original languageEnglish
Pages (from-to)40817-40825
Number of pages9
JournalJournal of Biological Chemistry
Volume287
Issue number48
DOIs
Publication statusPublished - 2012 Nov 23

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Soluble amyloid precursor protein 770 is released from inflamed endothelial cells and activated platelets: A novel biomarker for acute coronary syndrome'. Together they form a unique fingerprint.

Cite this