Plasma concentration of SCUBE1, a novel platelet protein, is elevated in patients with acute coronary syndrome and ischemic stroke.
OBJECTIVE
This study investigates the potential application of plasma SCUBE1 [signal peptide-CUB (complement C1r/C1s, Uegf, and Bmp1)-EGF (epidermal growth factor)-like domain-containing protein 1] as a biomarker of platelet activation in acute coronary syndrome (ACS) and acute ischemic stroke (AIS).


BACKGROUND
Platelet activation plays a crucial role in ACS and AIS. Platelet stimulation is associated with increased plasma concentration of SCUBE1, a novel platelet-endothelial secreted protein identified in our previous study.


METHODS
Plasma concentrations of SCUBE1 from 40 ACS and 40 AIS patients were measured by enzyme-linked immunoadsorbent assay and compared with the levels of 40 healthy control subjects and 83 chronic coronary artery disease (CAD) patients. Two-dimensional electrophoresis followed by Western blotting was used to characterize SCUBE1 protein in patients' plasma.


RESULTS
Plasma SCUBE1 concentration was virtually undetectable in healthy control subjects and CAD patients, but was significantly higher in ACS and AIS patients (median = 205 and 95.1 ng/ml, respectively, p < 0.01). The increase in plasma SCUBE1 was detectable in the plasma as early as 6 h after the onset of symptoms and remained detectable up to 84 h. Plasma SCUBE1 concentration is an independent predictor of stroke severity based on National Institutes of Health Stroke Scale (beta = 3.18, p < 0.001). Furthermore, smaller SCUBE1 fragments were detected in ACS patients' plasma, suggesting that plasma SCUBE1 might subject to a proteolytic regulation under pathological conditions.


CONCLUSIONS
Plasma SCUBE1 concentration is significantly elevated in ACS and AIS but not CAD patients. Plasma SCUBE1 is a potential biomarker of platelet activation in acute thrombotic disease.
Section of Cardiology, Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.
Dao-Fu
DF
Dai
Peterus
P
Thajeb
Cheng-Fen
CF
Tu
Fu-Tien
FT
Chiang
Chien-Hsiun
CH
Chen
Ruey-Bing
RB
Yang
Jin-Jer
JJ
Chen
D054058:Acute Coronary Syndrome / Q000097:blood* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets; D002545:Brain Ischemia / Q000150:complications*; D002135:Calcium-Binding Proteins; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000097:blood*; D008875:Middle Aged; D010865:Pilot Projects; D015539:Platelet Activation; D010974:Platelet Aggregation; D011379:Prognosis; D020521:Stroke / Q000097:blood* / Q000209:etiology* / Q000503:physiopathology
D015415:Biomarkers; D002135:Calcium-Binding Proteins; D008565:Membrane Proteins; C469998:SCUBE1 protein, human