Abstract
Cardiovascular toxicity and diseases are phenomena that have a vastly detrimental impact on morbidity and mortality. The pathophysiology driving the development of these conditions is multifactorial but commonly includes the perturbance of reactive oxygen species (ROS) signalling, iron homeostasis and mitochondrial bioenergetics. The transcription factor nuclear factor erythroid 2 (NFE2)-related factor 2 (NRF2), a master regulator of cytoprotective responses, drives the expression of genes that provide resistance to oxidative, electrophilic and xenobiotic stresses. Recent research has suggested that stimulation of the NRF2 signalling pathway can alleviate cardiotoxicity and hallmarks of cardiovascular disease progression. However, dysregulation of NRF2 dynamic responses can be severely impacted by ageing processes and off-target toxicity from clinical medicines including anthracycline chemotherapeutics, rendering cells of the cardiovascular system susceptible to toxicity and subsequent tissue dysfunction. This review addresses the current understanding of NRF2 mechanisms under homeostatic and cardiovascular pathophysiological conditions within the context of wider implications for this diverse transcription factor.