Reducing damage through Nrf-2

Abstract

This editorial refers to ‘Defective Nrf2-dependent redox signalling contributes to microvascular dysfunction in type 2 diabetes’ by G. V. Velmurugan et al ., pp. 143–150 , this issue and ‘Nrf2 deficiency prevents reductive stress-induced hypertrophic cardiomyopathy’ by S. Kannan et al ., pp. 63–73, this issue. Conventional wisdom has it that excessive oxidant stress usually causes tissue damage, with adverse cardiovascular remodelling. As a consequence, efforts have been amply developed to identify mechanisms and strategies to increase anti-oxidant defences. The transcription factor nuclear factor NF-E2-related factor 2 (Nrf2) has come into focus as a main regulator of the expression of anti-oxidant enzymes able to restore redox balance in the context of increased oxidant stress. However, as in many biological processes, dosage matters and too much of an apparently good thing can result in a catastrophe, as highlighted in the observations of two papers in this issue of Cardiovascular Research . The first paper by Velmurugan et al . started from the observation that reactive oxygen species (ROS) play an important role in the generation of myogenic tone in the microvasculature, i.e. in response to an acute increase in intraluminal pressure, vessels produce a burst of ROS that increases vessel contraction, as demonstrated in their study. This phenomenon is amplified in diabetes (type I and II), which is also associated with excessive production of various oxidant radicals; the latter may result from the dysregulation of the anti-oxidant defence mechanisms normally orchestrated by Nrf-2, which is reduced in diabetes.1 Therefore, the authors examined the hypothesis that excessive ROS contribute to microvascular dysfunction in a mouse type II diabetes model (db/db …