title: Nuclear factor (erythroid-derived 2)-like-2 factor (Nrf2), a key regulator of the antioxidant response to protect against atherosclerosis and nonalcoholic steatohepatitis.
abstract: Tissue oxidative stress is a common hallmark of atherosclerosis and non-alcoholic steatohepatitis (NASH), 2 conditions linked epidemiologically and pathophysiologically. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the master regulator of inducible antioxidant responses, that can attenuate cellular injury from oxidative stress induced by obesity and other redox insults. Nrf2 expression and activation is reduced in mouse and human vessels that harbor accelerated atherosclerosis and in livers with histologic criteria of NASH. Systemic antioxidants have thus been attractive therapeutic targets, but clinical trials have been largely unsuccessful in improving cardiovascular health. Macrophage-selective Nrf2 activation may, however, provide an approach to reduce vascular and hepatocyte injury without the complications of systemic antioxidants, since macrophages play key roles in the development and progression of both atherosclerosis and NASH. In this article, we review the common mechanisms of oxidative stress and inflammation in atherosclerosis and NASH, and discuss the role of Nrf2 in vascular and hepatocyte protection.
authors.affiliation: The Methodist Diabetes and Metabolism Institute, Center for Diabetes Research in The Methodist Hospital Research Institute, Weill Cornell Medical College, R8-111, 6670 Bertner Ave, Houston, 77030 TX, USA.
authors.forename: Anisha A
authors.initials: AA
authors.lastname: Gupte
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Lyon
authors.forename: Willa A
authors.initials: WA
authors.lastname: Hsueh
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism*; D005234:Fatty Liver / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D065626:Non-alcoholic Fatty Liver Disease; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; D020011:Protective Agents