title: Thioredoxins in cardiovascular disease.
abstract: Key thioredoxin (Trx) system components are nicotinamide adenine dinucleotide phosphate (NADPH), Trx reductase (TrxR), and Trx. TrxR catalyzes disulfide reduction in Trx with NADPH as cofactor. Because Trx is an antioxidant, oxidative stress results in an increase in Trx, which has a reduced disulfide component. If Trx is suppressed, oxidative stress in higher. In contrast a decrease in oxidative stress is associated with low Trx levels. Trx is involved in inflammation, apoptosis, embryogenesis, and cardiovascular disease (CVD). This review focuses on the Trx system in CVD. Abnormal Trx binding occurs in mouse familial combined hyperlipidemia; however, this has not been confirmed in humans. Congestive heart failure is a manifestation of many CVDs, which may be improved by attenuating oxidative stress through the suppression of Trx and decreased reactive oxygen species. Angiotensin II is associated with hypertension and other CVDs, and its receptor blockade results in decreased oxidative stress with reduced Trx levels. Inflammation is a major causative factor of CVDs, and myocarditis as an example, is associated with increased Trx levels. Vascular endothelial dysfunction has an association with CVD. This dysfunction is alleviated by hormone replacement therapy, which involves decreased oxidative stress and Trx levels. Diabetes mellitus has a major association with CVDs; increase in Trx levels may reflect insulin resistance. Identification of Trx system abnormalities may lead to innovative approaches to treat multiple CVDs and other pathologies.
authors.affiliation: a Gill Heart Institute, University of Kentucky, 326 Wethington Building, 900 South Limestone Street, Lexington, KY 40536-0200, USA.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Whayne
authors.affiliation: b Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Narasimham
authors.initials: N
authors.lastname: Parinandi
authors.affiliation: c Molecular Cardiology and Angiogenesis Laboratory, University of Connecticut School of Medicine, Farmington, Connecticut, USA.
authors.forename: Nilanjana
authors.initials: N
authors.lastname: Maulik
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology; D002318:Cardiovascular Diseases / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D003920:Diabetes Mellitus / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013879:Thioredoxins / Q000097:blood*
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; C491203:TXN protein, human; D013879:Thioredoxins
keywords: cardiovascular diseases; dérivés réactifs de l’oxygène; inflammation; maladies cardiovasculaires; oxidative stress; reactive oxygen species; stress oxydatif; thioredoxin; thioredoxin reductase; thiorédoxine; thiorédoxine réductase