Cyclophilin A: Novel biomarker for oxidative stress and cardiovascular diseases

Abstract

Intracellular redox status is closely regulated by the balance between oxidant and antioxidant systems, and their imbalance can cause oxidative or reductive stress, leading to cellular damage and dysregulation. Excessive reactive oxygen species (ROS) deteriorates vascular functions and promotes vascular diseases through multiple pathways. Recently, cyclophilin A (CyPA) has been shown to be secreted from vascular smooth muscle cells (VSMC) and to augment the destructive effects of ROS, linking it to the development of many cardiovascular diseases. In the secretion of CyPA, Rho-kinase plays an important role to organize vicious cycle for augmentation of ROS. The important role of Rho-kinase has been established in the pathogenesis of vasospasm, arteriosclerosis, ischemia/reperfusion injury, hypertension, pulmonary hypertension, stroke, and heart failure. Thus, it is important to understand Rho-kinase signaling and the role of downstream effectors such as CyPA in the vascular system in order to develop new therapeutic strategies for cardiovascular diseases. Here, we reported that plasma CyPA levels are increased in patients with coronary artery disease (CAD). Plasma CyPA levels were significantly higher in patients with significant coronary stenosis compared to those without it. A positive correlation was noted between plasma CyPA levels and significant coronary stenosis. The average number of stenotic coronary arteries and the need for coronary intervention were significantly increased in the quartiles of higher CyPA levels. Interestingly, plasma levels of CyPA increased according to the number of atherosclerotic risk factors, all of which induce oxidative stress. Furthermore, plasma levels of CyPA significantly reduced after medical treatment of risk factors. In this chapter, we will discuss the roles of VSMC-derived CyPA in promoting vascular diseases, with particular emphasis on the role of CyPA as a novel biomarker for CAD. Additionally, we will mention the beneficial effects of fasudil, a selective Rho-kinase inhibitor, for the treatment of cardiovascular diseases.