Title:Regression of Oxidative Stress by Targeting eNOS and Nrf2/ARE Signaling: A Guided Drug Target for Cardiovascular Diseases
Volume: 15
Issue: 9
Author(s): Tharmarajan Ramprasath, Varadaraj Vasudevan, Sundaresan Sasikumar, Shanavas Syed Mohamed Puhari, Luciano Saso and Govindan Sadasivam Selvam
Affiliation:
Keywords:
CVD, Endothelial dysfunction, eNOS, Nitric oxide, Nrf2/ARE, Phase II antioxidant enzymes.
Abstract: Cardiovascular diseases (CVDs) are the major health concern and the leading cause of death. Imbalance between
free radicals and anti-oxidant defence is associated with cellular dysfunctions leading to the pathophysiology of
various diseases including cardiac and vascular diseases. The stress responsive transcription factor NF-E2-related factor
2/antioxidant response element (Nrf2/ARE) regulates the expression of many detoxifying genes. Nitric oxide (NO) produced
by endothelial nitric oxide synthase (eNOS) is an important regulator of vascular function. Involvement of NO in
modulating Nrf2 signaling is well established. Thus, it is apparent that increasing NO bioavailability and antioxidant
status in vascular and myocardial tissue can be considered as a potential strategy to prevent the onset of vascular dysfunction
and CVDs and is therefore of therapeutical interest. Based on the marked protective effect of Nrf2/ARE signalling and
intriguing links between antioxidant mechanism and endothelial derived NO, the aim of the present review is to compile
conclusive evidence for the involvement of NO-Nrf2/ARE axis in the regulation of cardiovascular function. This review
also discusses on improving eNOS and Nrf2 signalling by Nrf2 activators which holds promise for countering cardiac and
vascular disorders.
