Role of Nrf2 antioxidant gene expression in cardiovascular disease

  • Research type

    Research Study

  • Full title

    Nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2) antioxidant gene expression and its role in combatting oxidative stress and maintaining vascular function in patients with cardiovascular disease.

  • IRAS ID

    269689

  • Contact name

    Faisel Khan

  • Contact email

    f.khan@dundee.ac.uk

  • Sponsor organisation

    University of Dundee

  • Duration of Study in the UK

    2 years, 0 months, 2 days

  • Research summary

    Oxidative or metabolic stress due to overproduction of reactive oxygen species (ROS) impairs myocardial perfusion (oxygen delivery to the heart) and promotes atherosclerosis. Ischaemia followed by reperfusion, after percutaneous coronary intervention (PCI) in patients admitted to hospital with acute coronary syndromes (ACS) (e.g. ST-elevated-myocardial infraction (STEMI), as denoted, heart attacks), further increases ROS production. This can lead to many adverse consequences, making patients vulnerable to re-infarction. Oxidative stress arises when ROS generation exceeds the capacity of antioxidant defense systems and can occur as a result of increased ROS production and/or impaired antioxidant capacity. Cells contain transcription factors that allow them to adapt to oxidative stress. Chief amongst these is NF-E2-related factor 2 (Nrf2), a master regulator of redox homeostasis. Nrf2 activity is increased in response to oxidative stress, resulting in induction of around 200 genes. Loss of Nrf2 signalling pathway has been closely linked with endothelial dysfunction and atherosclerosis. Accordingly, strategies to reduce oxidative stress and improve endothelial function could be beneficial. This prospective cohort study aims to recruit 40 patients with STEMI, undergoing PCI and 40 health volunteers to provide evidence that reduction in Nrf2 activity is associated with increased oxidative stress and poor vascular function in STEMI patients. Vascular tests such as laser perfusion imaging with iontophoresis, EndoPAT (to measure endothelial function) and sphygmoCor (to asses arterial stiffness) will be performed in both groups to determine the health of the blood vessels. Moreover, we will screen blood borne metabolic and inflammatory markers and conduct ex-vivo studies in human peripheral blood mononuclear cells (PBMCs) to provide a ‘proof of principle’ that the Nrf2 antioxidant system can be activated by therapeutic drugs and inducers.

  • REC name

    East of Scotland Research Ethics Service REC 2

  • REC reference

    19/ES/0103

  • Date of REC Opinion

    24 Oct 2019

  • REC opinion

    Further Information Favourable Opinion