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CLINICAL RESEARCH: BIOMARKER

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

Dao-Fu Dai, MD^_*,, Peterus Thajeb, MD^,, Cheng-Fen Tu, MS^¶, Fu-Tien Chiang, MD, PhD^_*, Chien-Hsiun Chen, PhD^¶, Ruey-Bing Yang, PhD^||,¶,_* and Jin-Jer Chen, MD^_*,¶,_*

^_* Section of Cardiology, Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan
Section of Cardiology, Department of Internal Medicine, Taoyuan General Hospital Department of Health Executive Yuan, Taipei, Taiwan
Department of Neurology and Medical Research, Mackay Memorial Hospital and Taipei Medical University, Taipei, Taiwan
Department of Biomedical Sciences, John A. Burns School of Medicine, University of Hawaii at Manoa, Manoa, Hawaii
^|| Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan
^¶ Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.

Manuscript received October 25, 2007; revised manuscript received December 19, 2007, accepted January 7, 2008.

^_* Reprint requests and correspondence: Dr. Jin-Jer Chen or Dr. Ruey-Bing Yang, Institute of Biomedical Sciences, Academia Sinica, 128 Academia Road, Sec. 2, Taipei 11529, Taiwan. (Email: rbyang{at}ibms.sinica.edu.tw).

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.

Abbreviations and Acronyms   ACS = acute coronary syndromes   AIS = acute ischemic stroke   CAD = coronary artery disease   CUB = complement proteins C1r/C1s, Uegf, and Bmp1   EGF = epidermal growth factor   LAT = large-vessel atherothrombotic (stroke)   NIHSS = National Institutes of Health Stroke Scale   NSTEMI = non–ST-segment elevation myocardial infarction   SCUBE1 = signal peptide–complement proteins C1r/C1s, Uegf, and Bmp1–epidermal growth factor-like domain containing protein 1   STEMI = ST-segment elevation myocardial infarction   TIA = transient ischemic attack   UA = unstable angina

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