Oxidants and Antioxidants Interplay in the Modulation of Inflammation and Cardiovascular Disease

Oxidative stress and inflammation are parallel self-perpetuating mechanisms that when triggered, appear to be strongly linked with several complications of cardiovascular disease (CVD). Unchecked production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) are largely the responsible factors that operate via the activation of several transcriptional messengers and a series of inflammatory pathways. Such messengers include Nuclear Factor-KappaB, known to contribute to a plethora of pathological complications such as endothelial dysfunction, the initiation and progression of atherosclerosis, irreversible ischemic reperfusion injury, and arrhythmias, particularly atrial fibrillation. Although much is known about the link between oxidative stress and CVD, the development of direct therapeutic interventions has remained elusive. In experimental animal models, the use of antioxidants in the form of dietary supplements has been shown to quench ROS/RNS or catalyse the break-up of free radical chains and has resulted in some measure of success. However, these findings have not been able to be replicated in human clinical trials for several different well-known agents, such as vitamin E and beta-carotene. Many potent naturally occurring antioxidants have been exploited by nature such as the oxygenated carotenoids (xanthophylls) and researchers have tested several of them in their natural form in clinical trials but sadly many of them have not translated into useful therapeutic tools. Questions, therefore, remain as to whether the reasons may be solely the inability to find the “right” compound(s) or delivery strategy, or the exact mechanisms of action of existing compounds have unknown targets or whether correct dosages are used. This chapter reviews existing evidence on the thesis that antioxidant/anti-inflammatory compounds may present an opportunity for the development of future therapeutic agents for both cardiovascular oxidative stress and inflammation. 

Keywords: Antioxidants, Cardiovascular disease, Ischaemia reperfusion injury, Leukocyte activation, Myocardial infarction, Oxidative stress.