Dual roles of vascular-derived reactive oxygen species--with a special reference to hydrogen peroxide and cyclophilin A.

Reactive oxygen species (ROS) have been considered to play a major role in the pathogenesis of cardiovascular diseases. However, this notion needs to be revised since recent evidence indicates that vascular-derived hydrogen peroxide (H2O2) serves as an important signaling molecule in the cardiovascular system at its low physiological concentrations. At low concentrations, H2O2 can act as a second messenger, transducing the oxidative signal into biological responses through post-translational protein modification. These structural changes ultimately lead to altered cellular function. 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. For example, excessive H2O2 deteriorates vascular functions and promotes vascular disease through multiple pathways. Furthermore, cyclophilin A (CyPA) has been shown to be secreted from vascular smooth muscle cells and to augment the destructive effects of ROS, linking it to the development of many cardiovascular diseases. Thus, it is important to understand the H2O2 signaling and the roles of downstream effectors such as CyPA in the vascular system in order to develop new therapeutic strategies for cardiovascular diseases. In this review, we will discuss the dual roles of vascular-derived H2O2 in mediating vascular functions (physiological roles) and promoting vascular diseases (pathological roles), with particular emphasis on the function of CyPA. This article is part of a Special Issue entitled "Redox Signalling in the Cardiovascular System".