Abstract 281: Cyclophilin A is a Novel Biomarker for Oxidative Stress and Atherosclerotic Diseases
Background We have recently demonstrated that oxidative stress induces secretion of cyclophilin A (CyPA) from vascular smooth muscle cells, which plays a crucial role in the pathogenesis of atherosclerosis and abdominal aortic aneurysms (AAA) in mice. Thus, we tested our hypothesis that plasma CyPA levels could be a biomarker of atherosclerotic diseases such as coronary artery disease (CAD) and AAA in humans.
Methods and Results In consecutive 320 patients undergoing coronary angiography, we examined the relationship between the severity of CAD and plasma CyPA levels measured by an immunoassay. Plasma CyPA levels were significantly higher in patients with significant coronary stenosis (>50%, n=189) compared to those without it (n=131) (P<0.001). A significant positive correlation was noted between plasma CyPA levels and significant coronary stenosis even after adjustment for age, sex, hypertension, diabetes, dyslipidemia and smoking. The average number of coronary arteries with significant stenosis and the need for coronary intervention were significantly increased in the quartiles of higher CyPA levels (both P<0.001). In addition, plasma CyPA levels were significantly correlated with the number of coronary arteries with significant stenosis (P<0.001). Indeed, plasma CyPA levels were a strong predictor of CAD (adjusted odds ratio for CAD, 6.20; 95% confidence interval, 3.14-12.27; P<0.001). Interestingly, plasma levels of CyPA increased according to the number of atherosclerotic risk factors that enhance oxidative stress. Furthermore, plasma CyPA levels significantly reduced after medical treatment of those risk factors. Finally, pathological examinations showed that CyPA was strongly expressed in atherosclerotic coronary plaque of patients with myocardial infarction. In a separate study, we examined the plasma CyPA levels in patients with aortic aneurysms. Plasma CyPA levels were significantly higher in patients with aortic aneurysms (n=58) compared to those without it (n=69) (P<0.001). Importantly, plasma CyPA levels were significantly higher in patients coexisting with CAD (n=18) compared to those only with aortic aneurysms (n=40) (P=0.012).
Conclusion Plasma CyPA level is a novel biomarker of atherosclerotic diseases.
- © 2013 by American Heart Association, Inc.