title: Soluble amyloid precursor protein 770 is released from inflamed endothelial cells and activated platelets: a novel biomarker for acute coronary syndrome.
abstract: BACKGROUND
  Separate monitoring of the cleavage products of different amyloid β precursor protein (APP) variants may provide useful information.
  
  
  RESULTS
  We found that soluble APP770 (sAPP770) is released from inflamed endothelial cells and activated platelets as judged by ELISA.
  
  
  CONCLUSIONS
  sAPP770 is an indicator for endothelial and platelet dysfunctions.
  
  
  CONCLUSIONS
  How sAPP770 is released in vivo has been shown. 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.
authors.affiliation: Disease Glycomics Team, RIKEN Advanced Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. shinobuk@riken.jp
authors.forename: Shinobu
authors.initials: S
authors.lastname: Kitazume
authors.forename: Akiomi
authors.initials: A
authors.lastname: Yoshihisa
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Yamaki
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Oikawa
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Tachida
authors.forename: Kazuko
authors.initials: K
authors.lastname: Ogawa
authors.forename: Rie
authors.initials: R
authors.lastname: Imamaki
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Hagiwara
authors.forename: Noriaki
authors.initials: N
authors.lastname: Kinoshita
authors.forename: Yasuchika
authors.initials: Y
authors.lastname: Takeishi
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Furukawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Tomita
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arai
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Iwata
authors.forename: Takaomi
authors.initials: T
authors.lastname: Saido
authors.forename: Naomasa
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Taniguchi
mesh_terms: D054058:Acute Coronary Syndrome / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism*; D015539:Platelet Activation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D010446:Peptide Fragments; C093596:amyloid beta-protein precursor 770 (301-323)