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Proteomic analysis of plasma in coronary artery disease patients: up-regulation of carboxypeptidase N1
차의과학 대학교 혈전/혈관생화학 연구실¹ , 연세의대 강남 세브란스병원 심장내과²
양정희¹ , 민필기² , 이병권² , 권혁문² , 정광회¹
Coronary artery disease (CAD), a leading cause of morbidity and mortality in the developed countries, has been known to be mainly associated with the presence and rupture of atherosclerotic plaques in the coronary arteries. In this study, we performed proteomic analysis to identify reliable biomarkers for the early detection of vulnerable risky individuals and to intervene promptly in progression of CAD. Twelve plasma samples of CAD patients versus 9 pooled plasma of normal control were analyzed by 2-Dimensional Electrophoresis (2-DE) followed by MALDI-TOF-Mass Spectrophotometry. Nine proteins upregulated more than 1.7 fold in CAD patients compared with normal were identified as follows: complement factor B preproprotein, transferrin, apolipoprotein –H, fibrinogen beta chain preprotein, prealbumin, gelsolin-a, complement component 4 binding protein, hemopexin, and carboxypeptidase N1 (CPN1). In validation studies by ELISA, we examined plasma samples of 29 normal control, 31 stable angina, 31 unstable angina, and 14 ST elevation myocardial infarction (STEMI) patients. We confirmed that CPN1, a metalloprotease which activates chemokine and known as a family of thrombin activated fibrinolysis inhibitor (TAFI), was overexpressed in plasma of ST segment elevation myocardial infarction (STEMI). The expression levels of CPN1 in normal control was 8.4± 2.45 ng/ml (n=29), stable angina was 6.8± 2.1ng/ml (n=31), unstable angina was 10.5± 2.3 ng/ml (n=31), and STEMI was 50.5± 25.34 ng/ml (n=14), respectively (p=0.001). Our results suggest that CPN1 may be a useful diagnostic and prognostic biomarker in patients of STEMI. Key words: Coronary artery disease, biomarker, proteomic analysis, carboxypeptidase N1
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