Title:Oxidative Stress and Cardiovascular Aging: Interaction Between NRF-2 and ADMA
Volume: 13
Issue: 3
Author(s): Nandini Nair*Enrique Gongora
Affiliation:
- Division of Cardiology, Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430,United States
Keywords:
NRF-2, ADMA, DDAH, oxidative stress, nitric oxide (NO), homeostasis.
Abstract: Background: The concept of antioxidant therapies assumes high importance as oxidative
stress is associated with cardiovascular aging via endothelial dysfunction. This review focuses on
exploring the interaction between nrf-2 and ADMA in influencing the nitric oxide pathway and cardiovascular
function.
Objective: A systematic review of literature from 1990 to 2016 was conducted using Pubmed and
Google Scholar. The literature suggests a strong influence of nrf-2 activation on up regulation of
DDAH I which degrades ADMA, the endogenous inhibitor of nitric oxide synthase. The resulting
decrease of ADMA would in turn enhance nitric oxide (NO) production. This would support endothelial
function by adequate NO production and homeostasis of endothelial function.
Conclusion: As NO production has many positive pleiotropic effects in the cardiovascular system,
such an interaction could be utilized for designing molecular therapeutics. The targets for therapy
need not be limited to activation of nrf-2. Modulation of molecules downstream such as DDAH I
can be used to regulate ADMA levels. Most current literature is supported by animal studies. The
concept of antioxidant therapies needs to be tested in well-defined randomized control trials. The
biochemical basis of nrf-2 activation needs to be substantiated in human studies.
