Nrf2 in early vascular ageing: calcification, senescence and therapy

Publication date: Available online 22 February 2020Source: Clinica Chimica ActaAuthor(s): Samsul Arefin, Sarah Buchanan, Sam Hobson, Julia Steinmetz, Shno Alsalhi, Paul G Shiels, Karolina Kublickiene, Peter StenvinkelAbstractUnder normal physiological conditions, free radical generation and antioxidant defences are balanced, and reactive oxygen species (ROS) usually act as secondary messengers in a plethora of biological processes. However, when this balance is impaired, oxidative stress develops due to imbalanced redox homeostasis resulting in cellular damage. Oxidative stress is now recognized as a trigger of cellular senescence, which is associated with multiple chronic 'burden of lifestyle' diseases, including atherosclerosis, type-2 diabetes, chronic kidney disease and vascular calcification; all of which possess signs of early vascular ageing.Nuclear factor erythroid 2-related factor 2 (Nrf2), termed the master regulator of antioxidant responses, is a transcription factor found to be frequently dysregulated in conditions characterized by oxidative stress and inflammation. Recent evidence suggests that activation of Nrf2 may be beneficial in protecting against vascular senescence and calcification. Both natural and synthetic Nrf2 agonists have been introduced as promising drug classes in different phases of clinical trials. However, overexpression of the Nrf2 pathway has also been linked to tumorigenesis, which highlights the requirement for further understanding of path...
Source: Clinica Chimica Acta - Category: Laboratory Medicine Source Type: research