Thioredoxins in cardiovascular disease

• Published in: Canadian journal of physiology and pharmacology Vol. 93; no. 11; p. 903
• Main Authors: Whayne, Jr, Thomas F, Parinandi, Narasimham, Maulik, Nilanjana
• Format: Journal Article
• Language: English
• Published: Canada 01-11-2015
• Subjects: Animals; Antioxidants - metabolism; Apoptosis - physiology; Cardiovascular Diseases - blood; Cardiovascular Diseases - diagnosis; Cardiovascular Diseases - epidemiology; Diabetes Mellitus - blood; Diabetes Mellitus - diagnosis; Diabetes Mellitus - epidemiology; Humans; Insulin Resistance - physiology; Reactive Oxygen Species - metabolism; Thioredoxins - blood; dérivés réactifs de l’oxygène; inflammation; thioredoxin; reactive oxygen species; thiorédoxine réductase; thiorédoxine; cardiovascular diseases; maladies cardiovasculaires; oxidative stress; stress oxydatif; thioredoxin reductase
• ISSN: 1205-7541
• DOI: 10.1139/cjpp-2015-0105

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.