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

RIKEN Advanced Science Institute, Japan
Journal of Biological Chemistry (Impact Factor: 4.57). 10/2012; 287(48). DOI: 10.1074/jbc.M112.398578
Source: PubMed


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.

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Available from: Noriaki Kinoshita, Jan 13, 2016
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    • "Soluble amyloid β precursor protein (APP) is rapidly released from activated platelets. Therefore APP could be an indicator for endothelial injury and platelet activation leading to fibrous plaque disruption and thrombus formation [79]. APP cleavage and release from activated platelets requires PKC activity and is regulated by the intracellular second messengers; phosphatidylinositol 2-phosphate and Ca 2+ . "
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