• free radicals
• redox signalling
• gene expression
• cardiovascular disease

• MAPKs, mitogen activated protein kinases
• NO, nitric oxide
• NOS, nitric oxide synthases
• ROS, reactive oxygen species
• SOXF, secreted oxidative stress induced factors

The generation of reactive oxygen species (ROS) is an inevitable consequence of life in an aerobic environment. ROS are characterised by their high chemical reactivity and include both free radicals (that is, species with one or more unpaired electrons, such as superoxide (O₂^.−) and hydroxyl radicals (OH^.)), and non-radical species such as hydrogen peroxide (H₂O₂). In health, there is a balance between ROS generation and the activity of enzymatic and non-enzymatic antioxidant systems that scavenge or reduce ROS concentrations.¹ Redox imbalance caused by increased ROS production and/or reduced antioxidant reserve causes oxidative stress—that is, an enhanced susceptibility of biological molecules and membranes to reaction with ROS.

Traditionally, oxidative stress has been considered deleterious due to free radical induced oxidation and damage of macromolecules, membranes and DNA. ROS generation by phagocytic cells such as neutrophils is a pivotal component of their antimicrobial actions and as such deleterious for ingested organisms, but is, however, clearly beneficial for the host. On the other hand, the restoration of oxygen supply during myocardial reperfusion after prolonged ischaemia is accompanied by a burst of free radical production that is damaging for the heart.² Oxidative stress induced damage includes acceleration of cell death through apoptosis and necrosis, mechanisms that may also be of relevance in advanced heart failure.

Recently, however, it has been recognised that oxidative stress may exert more subtle modulatory effects. Firstly, the tightly regulated production of ROS can modulate the activity of diverse intracellular molecules and signalling pathways (a mechanism commonly termed “redox signalling”), with the potential to induce highly specific acute and chronic changes in cell phenotype.³ This use of oxygen species to transmit biological information provides at least a teleological explanation for the widespread occurrence of ROS even in health. Secondly, inactivation …