Plasma Concentration of SCUBE1, a Novel Platelet Protein, Is Elevated in Patients With Acute Coronary Syndrome and Ischemic Stroke

Objectives: 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 (β = 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. ? 2008 American College of Cardiology Foundation.