title: Regression of oxidative stress by targeting eNOS and Nrf2/ARE signaling: a guided drug target for cardiovascular diseases.
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.
authors.forename: Tharmarajan
authors.initials: T
authors.lastname: Ramprasath
authors.forename: Varadaraj
authors.initials: V
authors.lastname: Vasudevan
authors.forename: Sundaresan
authors.initials: S
authors.lastname: Sasikumar
authors.forename: Shanavas Syed Mohamed
authors.initials: SS
authors.lastname: Puhari
authors.forename: Luciano
authors.initials: L
authors.lastname: Saso
authors.affiliation: Department of Biochemistry, Center for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai 625021, Tamil Nadu, India. drselvamgsbiochem@rediffmail.com.
authors.forename: Govindan Sadasivam
authors.initials: GS
authors.lastname: Selvam
mesh_terms: D000818:Animals; D061745:Antioxidant Response Elements / Q000187:drug effects*; D000975:Antioxidants / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D055808:Drug Discovery; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III