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(Hypertension. 2009;54:224.)
© 2009 American Heart Association, Inc.

Editorial Commentaries

Mitochondrial Thioredoxin

Novel Regulator for NADPH Oxidase and Angiotensin II-Induced Hypertension

Tohru Fukai

From the Section of Cardiology, Department of Medicine, and Department of Pharmacology, University of Illinois at Chicago.

Correspondence to Tohru Fukai, Departments of Medicine (Section of Cardiology) and Pharmacology, Center for Cardiovascular Research, University of Illinois at Chicago, 835 S Wolcott, M/C868, E403MSB, Chicago, IL 60612. E-mail tfukai@uic.edu

An extract of the first 250 words of the full text is provided, because this article has no abstract.

The source of reactive oxygen species (ROS) produced in cardiovascular systems includes NADPH oxidase, xanthine oxidase, and uncoupling of endothelial NO synthase (eNOS) as well as mitochondria. In particular, NADPH oxidase has been considered a predominant source of ROS in the pathogenesis of hypertension, atherosclerosis, cardiac hypertrophy, and heart failure. Recent data suggest that angiotensin (Ang) II, a potent hypertensive hormone which is known to activate NADPH oxidase, induces mitochondrial dysfunction, which, in turn, promotes excess amounts of ROS, eg, superoxide (O₂^·–), hydrogen peroxide (H₂O₂), and peroxynitrite from mitochondria.¹ This contributes to endothelial dysfunction by reducing NO bioavailability and activating apoptotic signaling, thereby progressing cardiovascular disease, neurodegenerative disease, and aging. The role of mitochondrial ROS is demonstrated by previous reports that transgenic mice overexpressing catalase targeted to the mitochondria exhibit an extended life span.² Mice overexpressing peroxiredoxin 3, the mitochondria-specific peroxidase linked to thioredoxin 2 (Trx2), show improved survival after myocardial infarction.³ Furthermore, Ang II-converting enzyme inhibitors and Ang II type I receptor blockers prevent age-related mitochondrial dysfunction, hypertension-induced renal mitochondrial dysfunction, and cardiac mitochondrial dysfunction in the setting of acute ischemia.¹ However, the role of mitochondria-derived ROS and its relationship with NADPH oxidase-derived ROS in Ang II-induced hypertension remain unclear.

One of the major antioxidant defense systems against mitochondrial ROS (in particular, H₂O₂) is thiol-reducing systems, including thioredoxin (Trx), glutaredoxin, and the glutathione system. The Trx system (Trx, Trx reductase, and NADPH) reduces oxidized cysteine groups on protein through an interaction with the redox-active . . . [Full Text of this Article]

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