Hyperglycaemia Inhibits Thioredoxin-Mediated Angiogenesis: Implications for Impairment of Neovascularisation in Diabetes Mellitus

Buckle, Andrew; Dunn, Louise; Ng, M.

doi:10.1016/j.hlc.2007.06.512

Cited by 3 publications

(5 citation statements)

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“…Downregulation of TRX1 by siRNA in human coronary artery ECs inhibited migration and vascular network formation in a Matrigel assay, while siRNA inhibition of TXNIP increased migration and vascular network formation. 90 …”

Section: The Thioredoxin Systemmentioning

confidence: 99%

“…103 A carbohydrate response element within the TXNIP promoter underlies this striking feature. 104 Thioredoxin interacting protein is induced by sugars in a variety of other cell types including vascular smooth muscle cells, 105 ECs, 90, 106 hepatoma, 107 and breast cancer. 21 It is associated with increased apoptosis in pancreatic beta islets 108, 109 and cardiomyocytes by competitive inhibition of the TRX1/ASK-1 complex.…”

Section: The Thioredoxin Systemmentioning

confidence: 99%

“…93, 110, 111 Hyperglycemic induction of TXNIP in vascular smooth muscle cells and ECs in vitro represses TRX activity, induces ROS accumulation, 105 and inhibits vascular network formation. 90 Knockdown of TXNIP by siRNA or adenoviral overexpression of TRX1 abrogates glucose-induced ROS accumulation in smooth muscle cells. 105 Furthermore, in streptozotocin-induced diabetic rats, TXNIP expression was increased in the vasculature and TRX activity reduced.…”

Section: The Thioredoxin Systemmentioning

confidence: 99%

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The Emerging Role of the Thioredoxin System in Angiogenesis

Dunn

Buckle

Cooke

et al. 2010

ATVB

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Notwithstanding a multitude of studies, the mechanisms of angiogenesis remain incompletely understood. Increasing evidence suggests that cellular redox homeostasis is an important regulator of angiogenesis. The thioredoxin (TRX) system functions as an endogenous antioxidant that can exert influence over endothelial cell (EC) function via modulation of cellular redox status. It has become apparent that the cytosolic thioredoxin-1 (TRX1) isoform participates in both canonical and novel angiogenic signaling pathways, and may represent an avenue for therapeutic exploitation. Recent studies have further identified a role for the mitochondrial isoform thioredoxin-2 (TRX2) in ischemia-induced angiogenesis. Thioredoxin interacting protein (TXNIP) is the endogenous inhibitor of TRX redox activity that has been implicated in growth factor-mediated angiogenesis. As TXNIP is strongly induced by glucose, this molecule could be of consequence to disordered angiogenesis manifest in diabetes mellitus. This review will focus on data implicating the TRX system in EC homeostasis and angiogenesis.

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Section: The Thioredoxin Systemmentioning

confidence: 99%

Section: The Thioredoxin Systemmentioning

confidence: 99%

Section: The Thioredoxin Systemmentioning

confidence: 99%

See 1 more Smart Citation

The Emerging Role of the Thioredoxin System in Angiogenesis

Dunn

Buckle

Cooke

et al. 2010

ATVB

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“…On the contrary side, there are several evidences indicating TXNIP suppress angiogenic events in ECs exposed to diabetic-like environment. In this line, high glucose exposure to endothelial progenitor cells is reported to impair EC proliferation, migration, and tube formation which is efficiently ameliorated by TXNIP silencing by siRNA [178, 179]. According to further in vitro experimentations, TXNIP has been suggested to mediate HG-induced impairment by abolishing VEGF production and angiogenic effects in diabetic conditions, which requires adequate TRX1 activity [180].…”

Section: Introductionmentioning

confidence: 99%

Thioredoxin-Interacting Protein (TXNIP) in Cerebrovascular and Neurodegenerative Diseases: Regulation and Implication

2018

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Neurological diseases, including acute attacks (e.g., ischemic stroke) and chronic neurodegenerative diseases (e.g., Alzheimer's disease), have always been one of the leading cause of morbidity and mortality worldwide. These debilitating diseases represent an enormous disease burden, not only in terms of health suffering but also in economic costs. Although the clinical presentations differ for these diseases, a growing body of evidence suggests that oxidative stress and inflammatory responses in brain tissue significantly contribute to their pathology. However, therapies attempting to prevent oxidative damage or inhibiting inflammation have shown little success. Identification and targeting endogenous "upstream" mediators that normalize such processes will lead to improve therapeutic strategy of these diseases. Thioredoxin-interacting protein (TXNIP) is an endogenous inhibitor of the thioredoxin (TRX) system, a major cellular thiol-reducing and antioxidant system. TXNIP regulating redox/glucose-induced stress and inflammation, now is known to get upregulated in stroke and other brain diseases, and represents a promising therapeutic target. In particular, there is growing evidence that glucose strongly induces TXNIP in multiple cell types, suggesting possible physiological roles of TXNIP in glucose metabolism. Recently, a significant body of literature has supported an essential role of TXNIP in the activation of the NOD-like receptor protein (NLRP3)-inflammasome, a well-established multi-molecular protein complex and a pivotal mediator of sterile inflammation. Accordingly, TXNIP has been postulated to reside centrally in detecting cellular damage and mediating inflammatory responses to tissue injury. The majority of recent studies have shown that pharmacological inhibition or genetic deletion of TXNIP is neuroprotective and able to reduce detrimental aspects of pathology following cerebrovascular and neurodegenerative diseases. Conspicuously, the mainstream of the emerging evidences is highlighting TXNIP link to damaging signals in endothelial cells. Thereby, here, we keep the trend to present the accumulative data on CNS diseases dealing with vascular integrity. This review aims to summarize evidence supporting the significant contribution of regulatory mechanisms of TXNIP with the development of brain diseases, explore pharmacological strategies of targeting TXNIP, and outline obstacles to be considered for efficient clinical translation.

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“…It is known that hyperglycemia induced oxidative stress modulated by TXNIP induction, with the consequent inhibition of the anti-oxidative function [28]. In addition, TXNIP is dramatically induced by glucose [27] and, in hyperglycemia, inhibits thioredoxin with accompanying impairment in vascular network formation [27,29].…”

Section: Discussionmentioning

confidence: 99%