Article

Thioredoxin in the cardiovascular system

Cardiovascular Research Institute, Department of Medicine, University of Rochester, Rochester, NY, USA.
Journal of Molecular Medicine (Impact Factor: 4.74). 01/2007; 84(12):997-1003. DOI: 10.1007/s00109-006-0109-6
Source: PubMed

ABSTRACT The thioredoxin (TRX) system (TRX, TRX reductase, and NADPH) is a ubiquitous thiol oxidoreductase system that regulates cellular reduction/oxidation (redox) status. The impairment of cell redox state alters multiple cell pathways, which may contribute to the pathogenesis of cardiovascular disorders including hypertension, atherosclerosis, and heart failure. In this manuscript, we review the essential roles that TRX plays by limiting oxidative stress directly via antioxidant effects and indirectly by protein-protein interactions with key signaling molecules such as thioredoxin interacting protein (TXNIP). TRX and its endogenous regulators may represent important future targets to develop clinical therapies for diseases associated with oxidative stress.

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    • "However, pathological dysregulation of the redox balance could contribute to CVDs [4] [5]. Cellular redox homeostasis is tightly regulated by the coordinated action of NADPH oxidases, the TRX system and glutathione (GSH) [6], among others. The TRX system and GSH are thiol reduction systems with a key role in the defense against excessive ROS production, as well as in the modulation of signaling processes such as inflammation, cellular proliferation, and apoptosis [7] [8] [9]. "
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    ABSTRACT: Cell stress proteins (CSPS) are a large and heterogeneous family of proteins, sharing two main characteristics: their levels and/or location are modified under stress and most of them can exert a chaperon function inside the cells. Nonetheless, they are also involved in the modulation of several mechanisms, both at the intracellular and the extracellular compartments. There are more than 100 proteins belonging to the CSPs family, among them the thioredoxin (TRX) system, which is the focus of the present paper. TRX system is composed of several proteins such as TRX and peroxiredoxin (PRDX), two thiol-containing enzymes that are key players in redox homeostasis due to their ability to scavenge potential harmful reactive oxygen species. In addition to their main role as antioxidants, recent data highlights their function in several processes such as cell signalling, immune inflammatory responses, or apoptosis, all of them key mechanisms involved in atherothrombosis. Moreover, since TRX and PRDX are present in the pathological vascular wall and can be secreted under prooxidative conditions to the circulation, several studies have addressed their role as diagnostic, prognostic, and therapeutic biomarkers of cardiovascular diseases (CVDs).
    Oxidative Medicine and Cellular Longevity 06/2012; 2012:232464. DOI:10.1155/2012/232464 · 3.36 Impact Factor
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    • "This protein inhibits the thioredoxin (TXN) system functioning as an endogenous inhibitor [10]. TXN is a multifunctional antioxidant enzyme expressed in various tissues [11] and plays an indirect, but essential, role in signaling molecules by protein–protein interactions [12]. To date, TXNIP gene has been identified as one of the most dramatically up-regulated genes in studies looking at the genomic effect of glucose on isolated islet cells [13]. "
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    ABSTRACT: To investigate the relationship between TXNIP polymorphisms, diabetes and hypertension phenotypes in the Brazilian general population. Five hundred seventy-six individuals randomly selected from the general urban population according to the MONICA-WHO project guidelines were phenotyped for cardiovascular risk factors. A second, independent, sample composed of 487 family-trios from a different site was also selected. Nine TXNIP polymorphisms were studied. The potential association between TXNIP variability and glucose-phenotypes in children was also explored. TXNIP expression was quantified by real-time PCR in 53 samples from human smooth muscle cells primary culture. TXNIP rs7211 and rs7212 polymorphisms were significantly associated with glucose and blood pressure related phenotypes. In multivariate logistic regression models the studied markers remained associated with diabetes even after adjustment for covariates. TXNIP rs7211 T/rs7212 G haplotype (present in approximately 17% of individuals) was significantly associated to diabetes in both samples. In children, the TXNIP rs7211 T/rs7212 G haplotype was associated with fasting insulin concentrations. Finally, cells harboring TXNIP rs7212 G allele presented higher TXNIP expression levels compared with carriers of TXNIP rs7212 CC genotype (p=0.02). Carriers of TXNIP genetic variants presented higher TXNIP expression, early signs of glucose homeostasis derangement and increased susceptibility to chronic metabolic conditions such as diabetes and hypertension. Our data suggest that genetic variation in the TXNIP gene may act as a "common ground" modulator of both traits: diabetes and hypertension.
    Atherosclerosis 03/2012; 221(1):131-6. DOI:10.1016/j.atherosclerosis.2011.12.009 · 3.97 Impact Factor
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    • "Thioredoxin has been recently proven to be crucial for maintaining activity of antioxidative enzymes [23] and plays a key role in the antiapoptotic signalling pathway [24]. In our study, this protection was evidenced by an increase in the Bcl-2/Bax protein expression ratio and suppressed apoptotic cells, especially apoptotic endothelial cells. "
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    ABSTRACT: Microvascular reflow is crucial for myocyte survival during ischaemia/reperfusion injury. We aimed to assess if salvianolate, a highly purified aqueous extract from Radix salviae miltiorrhizae, could improve impaired microvascular reflow induced by ischaemia/reperfusion injury, using a porcine closed-chest model. Left anterior descending coronary artery ligation was created by balloon occlusion for 2 h followed by reperfusion for 14 days. Salvianolate was administrated intravenously for 7 days at low dose (5 mg/kg/day), high dose (10 mg/kg/day) or high dose combined with one 20 mg intracoronary bolus injection just at the beginning of reperfusion. Control-group animals were only given the same volume of saline. After 14 days of reperfusion, animals treated with high-dose salvianolate showed improved myocardial perfusion assessed by real-time myocardial contrast echocardiography and coloured microspheres. The beneficial effect was further supported by increased capillary density and decreased infarct size. All these effects eventually resulted in well-preserved cardiac function detected by echocardiography. Moreover, we also demonstrated that salvianolate administration was associated with elevated superoxide dismutase activity, thioredoxin activity and glutathione concentration, and reduced malondialdehyde concentration, which, in turn, resulted in a significant decrease in terminal deoxynucleotide transferase-mediated dUTP nick end labelling-positive cells and an increased ratio of Bcl-2 to Bax expression. Intravenous salvianolate at a dose of 10 mg/kg/day for 7 days had significant beneficial effects on myocardial microvascular reflow, which were associated with decreased oxidative stress and apoptosis.
    Archives of cardiovascular diseases 05/2011; 104(5):313-24. DOI:10.1016/j.acvd.2011.02.004 · 1.66 Impact Factor
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