Oxidative Stress Markers Are Associated with Persistent Atrial Fibrillation

Neuman, Robert W.; Bloom, Heather; Shukrullah, Irfan; Darrow, Lyndsey A.; Kleinbaum, David G.; Jones, Dean P.; Dudley, Samuel C.

doi:10.1373/clinchem.2006.083923

Cited by 196 publications

(143 citation statements)

References 32 publications

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“…Oxidized plasma GSH/GSSG redox state has also been associated with Type 2 diabetes (151) and increased carotid intima media thickness, an early risk factor for cardiovascular disease (11). Other in vivo studies show that an oxidized Cys/CySS redox state is associated with increased persistent atrial fibrillation (132) and with myocardial perfusion defects (2). Together, with in vitro mechanistic studies, these clinical studies indicate that redox-dependent changes in peroxide are likely to be important components of CVD risk.…”

Section: Oxidative Stress As a Disruption Of Redox Signaling And Controlmentioning

confidence: 99%

Radical-free biology of oxidative stress

Jones¹

2008

American Journal of Physiology-Cell Physiology

1,019

839

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Free radical-induced macromolecular damage has been studied extensively as a mechanism of oxidative stress, but large-scale intervention trials with free radical scavenging antioxidant supplements show little benefit in humans. The present review summarizes data supporting a complementary hypothesis for oxidative stress in disease that can occur without free radicals. This hypothesis, which is termed the "redox hypothesis," is that oxidative stress occurs as a consequence of disruption of thiol redox circuits, which normally function in cell signaling and physiological regulation. The redox states of thiol systems are sensitive to twoelectron oxidants and controlled by the thioredoxins (Trx), glutathione (GSH), and cysteine (Cys). Trx and GSH systems are maintained under stable, but nonequilibrium conditions, due to a continuous oxidation of cell thiols at a rate of about 0.5% of the total thiol pool per minute. Redox-sensitive thiols are critical for signal transduction (e.g., H-Ras, PTP-1B), transcription factor binding to DNA (e.g., Nrf-2, nuclear factor-B), receptor activation (e.g., ␣IIb␤3 integrin in platelet activation), and other processes. Nonradical oxidants, including peroxides, aldehydes, quinones, and epoxides, are generated enzymatically from both endogenous and exogenous precursors and do not require free radicals as intermediates to oxidize or modify these thiols. Because of the nonequilibrium conditions in the thiol pathways, aberrant generation of nonradical oxidants at rates comparable to normal oxidation may be sufficient to disrupt function. Considerable opportunity exists to elucidate specific thiol control pathways and develop interventional strategies to restore normal redox control and protect against oxidative stress in aging and age-related disease.thioredoxin; glutathione; cysteine; hydrogen peroxide; redox signaling; protein thiol ONE OF THE GREAT REDOX BIOLOGISTS of the past century, Howard S. Mason, professed that to advance science, a scientist must interpret observations at the limit of their meaning. The present review of the redox biology of thiol systems addresses the possibility that disruption of the function and homeostasis of thiol systems is the most central feature of oxidative stress that contributes to mechanisms of aging and age-related disease. I have termed this the "redox hypothesis" to facilitate distinction from free radical hypotheses.Many proteins contain redox-sensitive thiols, and reactions of thiol systems occur largely by nonradical two-electron transfers. Accumulating data show that central thiol-disulfide couples are maintained under nonequilibrium conditions in biological systems. This presents a condition wherein changes in abundance and distribution of redox catalysts and changes in rates of generation of relevant oxidants (e.g., peroxides) and precursors for NADPH supply can account for pathological effects of oxidative stress through altered functions of enzymes, receptors, transporters, transcription factors, and structural elements, without free ra...

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Section: Oxidative Stress As a Disruption Of Redox Signaling And Controlmentioning

confidence: 99%

Radical-free biology of oxidative stress

Jones¹

2008

American Journal of Physiology-Cell Physiology

1,019

839

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“…In the context of cardiac disease, ample evidence exists for the existence of a pathogenic link between enhanced ROS production, mitochondrial dysfunction and the development of heart failure (Martin-Fernandez and Gredilla 2016). In addition, serum markers of oxidative stress have been found to be increased in patients with persistent atrial fibrillation (Neuman et al 2007). …”

Section: Mitochondrial Functionmentioning

confidence: 99%

Cardiac aging and heart disease in humans

2017

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The world population continues to grow older rapidly, mostly because of declining fertility and increasing longevity. Since age represents the largest risk factor for cardiovascular disease, the prevalence of these pathologies increases dramatically with increasing age. In order to improve patient care and prevention for age-related cardiac diseases, insight should be gained from the analysis of processes involved in and leading to cardiac aging. It is from this perspective that we provide here an overview of changes associated with age in the heart on four levels: functional, structural, cellular and molecular. We highlight those changes that are in common with the development of the two major age-associated cardiac pathologies: heart failure and atrial fibrillation. These commonly affected processes in aging and cardiac pathophysiology may provide an explanation for the age risk factor in cardiac disease.

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“…For example, the cloning of mammalian Trx2 occurred as late as 1997 [127], providing new insight in the compartmentalization of the Trx2 in mitochondria (mitochondria, Figure 5 right). Similarly, the Cys/CySS couple in the plasma has only slowly surfaced as a significant independent player in protein thiol oxidation, with relevance to clinical conditions such as cardiovascular disease [58,59,82,128] and alcoholic lung disease [129]. Furthermore, identification of novel protein targets that are regulated by redox state has been increasing as redox proteomic techniques improve [130][131][132].…”

Section: Perspectives For Redox Systems Biologymentioning

confidence: 99%

Nonequilibrium thermodynamics of thiol/disulfide redox systems: A perspective on redox systems biology

Kemp

Jones

2008

Free Radical Biology and Medicine

513

444

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Understanding the dynamics of redox elements in biologic systems remains a major challenge for redox signaling and oxidative stress research. Central redox elements include evolutionarily conserved subsets of cysteines and methionines of proteins which function as sulfur switches and labile reactive oxygen species (ROS) and reactive nitrogen species (RNS) which function in redox signaling. The sulfur switches depend upon redox environments in which rates of oxidation are balanced with rates of reduction through the thioredoxins, glutathione/glutathione disulfide and cysteine/cystine redox couples. These central couples, which we term redox control nodes, are maintained at stable but non-equilibrium steady states, are largely independently regulated in different subcellular compartments and are quasi-independent from each other within compartments. Disruption of the redox control nodes can differentially affect sulfur switches, thereby creating a diversity of oxidative stress responses. Systems biology provides approaches to address the complexity of these responses. In the present review, we summarize thiol/disulfide pathway, redox potential and rate information as a basis for kinetic modeling of sulfur switches. The summary identifies gaps in knowledge especially related to redox communication between compartments, definition of redox pathways and discrimination between types of sulfur switches. A formulation for kinetic modeling of GSH/GSSG redox control indicates that systems biology could encourage novel therapeutic approaches to protect against oxidative stress by identifying specific redox-sensitive sites which could be targeted for intervention.

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Oxidative Stress Markers Are Associated with Persistent Atrial Fibrillation

Cited by 196 publications

References 32 publications

Radical-free biology of oxidative stress

Radical-free biology of oxidative stress

Cardiac aging and heart disease in humans

Nonequilibrium thermodynamics of thiol/disulfide redox systems: A perspective on redox systems biology

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