Cardiac hypertrophy and oxidative stress: a leap of faith or stark reality?

Abstract

While the role of oxidative stress in diseases like hypercholesterolaemia, atherosclerosis, and diabetes is becoming increasingly well established, its involvement in the development of cardiac hypertrophy is more controversial It is well known that cardiovascular diseases such as hypertension, valvular dysfunction, and myocardial infarction are associated with cardiac hypertrophy, which is itself an independent risk factor for sudden death. Less certain, however, is the identity of the molecular mechanisms involved in the hypertrophic process. The role of oxidative stress in the pathophysiology of diseases like hypercholesterolaemia, atherosclerosis, and diabetes is becoming increasingly well established. In contrast, the involvement of oxidative stress in the development of cardiac hypertrophy is more controversial, though with the evidence now available this concept does not require the great leap of faith once envisaged. The term “oxidative stress” has become something of a buzz phrase in recent years, being implicated in countless disease processes. What is oxidative stress? It is described as a disturbance in the balance between the production of reactive oxygen species (ROS) and antioxidant defences in favour of the former. Examples of such ROS are superoxide anions (O2−), hydroxyl radicals, nitric oxide (NO) and peroxynitrite. Potential sources of these molecules include mitochondrial respiration, cytochrome p450s, xanthine oxidase, NAD(P)H oxidases, NO synthase, and others. In the current issue of Heart Hausse and colleagues1 (000) describe an interesting link between oxidative stress and the cardiac hypertrophy seen in the neurodegenerative disease Friedreich's ataxia (FRDA). In their study administration of the antioxidant idebenone, a short chain analogue of co-enzyme Q10, produced a significant reduction in cardiac hypertrophy in 50% of the study cohort. A further striking link between oxidative stress and the pathology of FRDA is highlighted in another autosomal …