Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor

Gryglewski, Ryszard J.; Palmer, Richard; Moncada, Salvador

doi:10.1038/320454a0

Cited by 2,271 publications

(1,137 citation statements)

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“…16 Oxidative stress plays an important role in the mechanism(s) of endothelial dysfunction in cardiovascular diseases. [17][18][19] Antioxidants have been shown to restore endothelial function in patients with coronary artery disease. 20,21 It is known that statins and ACE inhibitors improve endothelial function; 22,23 therefore, they may influence the thioredoxin levels at admission and during hospital stay and follow-up.…”

Section: Discussionmentioning

confidence: 99%

Increased plasma thioredoxin in patients with acute myocardial infarction

Soejima

Suefuji

Miyamoto

et al. 2003

Clinical Cardiology

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SummaryBackground and hypothesis: Thioredoxin is an important biomarker for oxidative stress. We investigated whether thioredoxin levels were elevated in patients with acute myocardial infarction (AMI) and were associated with the results of coronary reperfusion.Methods: The present study determined plasma thioredoxin levels in 51 patients with AMI, 30 patients with stable exertional angina (SEA), and 30 patients with chest pain syndrome (CPS). Plasma sampling was performed on admission, at 12 h, 1 week, 2 weeks, and 4 weeks in patients with AMI, and after admission in patients with SEA and CPS.Results: Plasma thioredoxin levels on admission were higher in patients with AMI than in those with SEA and CPS. Plasma thioredoxin levels in patients with AMI were decreased in 12 h without further change thereafter. However, thioredoxin levels in patients with AMI remained higher than in those with SEA. In multivariate analysis, higher levels of thioredoxin on admission were a risk factor for failure in emergent reperfusion therapy in patients with AMI independent of other factors.

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Section: Discussionmentioning

confidence: 99%

Increased plasma thioredoxin in patients with acute myocardial infarction

Soejima

Suefuji

Miyamoto

et al. 2003

Clinical Cardiology

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“…Other animal models of insulin resistance exhibit lower skeletal muscle guanylate cyclase activity [34,35]. NO reacts with superoxide radicals, thus lowering the effective NO available ; indeed, the superoxide scavenger superoxide dismutase increases the effectiveness of NO, and can, for example, promote vascular smooth muscle relaxation in itro [36]. The diabetic state is often associated with excessive superoxide radical production, leading to endothelial disfunction and macrovascular disease [37].…”

Section: Discussionmentioning

confidence: 99%

Evidence for altered sensitivity of the nitric oxide/cGMP signalling cascade in insulin-resistant skeletal muscle

Young

Leighton

1998

Biochemical Journal

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Nitric oxide activates guanylate cyclase to form cGMP, comprising a signalling system that is believed to be a distinct mechanism for increasing glucose transport and metabolism in skeletal muscle. The effects of a selective cGMP phosphodiesterase inhibitor, zaprinast, on basal glucose utilization was investigated in incubated rat soleus muscle preparations isolated from both insulin-sensitive (lean Zucker; Fa/?) and insulin-resistant (obese Zucker; fa/fa) rats. Zaprinast at 27 μM significantly increased cGMP levels in incubated soleus muscle isolated from lean, but not obese, Zucker rats. Muscles were incubated with 14C-labelled glucose and various concentrations of zaprinast (3, 27 and 243 μM). Zaprinast (at 27 and 243 μM) significantly increased rates of net and 14C-labelled lactate release and of glycogen synthesis in lean Zucker rat soleus muscle; glucose oxidation was also increased by 27 μM zaprinast. In addition, regardless of concentration, the phosphodiesterase inhibitor failed to increase any aspect of 14C-labelled glucose utilization in soleus muscles isolated from obese Zucker rats. The maximal activity of nitric oxide synthase (NOS) was significantly decreased in insulin-resistant obese Zucker muscles. Thus the lack of effect of zaprinast in insulin-resistant skeletal muscle is consistent with decreased NOS activity. To test whether there is a defect in insulin-resistant skeletal muscle for endogenous activation of guanylate cyclase, soleus muscles were isolated from both insulin-sensitive and insulin-resistant Zucker rats and incubated with various concentrations of the NO donor sodium nitroprusside (SNP; 0.1, 1, 5 and 15 mM). SNP significantly increased rates of net and 14C-labelled lactate release, as well as glucose oxidation in muscles isolated from both insulin-sensitive and insulin-resistant rats. A decreased response to SNP was observed in the dose-dependent generation of cGMP within isolated soleus muscles from insulin-resistant rats. A possible link between impaired NO/cGMP signalling and abnormal glucose utilization by skeletal muscle is discussed.

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“…[67][68][69] Superoxide is believed to react with endothelial nitric oxide to yield peroxynitrite, thereby limiting the normal vasodilation response. 70,71 Both superoxide and peroxynitrite contribute to the modification of tissues, resulting in the generation of lipid peroxides and in the case of peroxynitrite, the modification of proteins by tyrosine nitration and the formation of 3-nitrotyrosine. The recent findings that heme oxygenase-1 (HO-1) and glutathione peroxidase (GPx) expression and activity are impaired in cultured vascular endothelial cells treated with homocysteine suggest that HHcy can inhibit the antioxidant potential of cells.…”

Section: Oxidative Stressmentioning

confidence: 99%

Role of hyperhomocysteinemia in endothelial dysfunction and atherothrombotic disease

2004

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Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular disease, including ischemic heart disease, stroke, and peripheral vascular disease. Mutations in the enzymes responsible for homocysteine metabolism, particularly cystathionine b-synthase (CBS) or 5,10-methylenetetrahydrofolate reductase (MTHFR), result in severe forms of HHcy. Additionally, nutritional deficiencies in B vitamin cofactors required for homocysteine metabolism, including folic acid, vitamin B6 (pyridoxal phosphate), and/or B12 (methylcobalamin), can induce HHcy. Studies using animal models of genetic-and diet-induced HHcy have recently demonstrated a causal relationship between HHcy, endothelial dysfunction, and accelerated atherosclerosis. Dietary enrichment in B vitamins attenuates these adverse effects of HHcy. Although oxidative stress and activation of proinflammatory factors have been proposed to explain the atherogenic effects of HHcy, recent in vitro and in vivo studies demonstrate that HHcy induces endoplasmic reticulum (ER) stress, leading to activation of the unfolded protein response (UPR). This review summarizes the current role of HHcy in endothelial dysfunction and explores the cellular mechanisms, including ER stress, that contribute to atherothrombosis.

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Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor

Cited by 2,271 publications

References 14 publications

Increased plasma thioredoxin in patients with acute myocardial infarction

Increased plasma thioredoxin in patients with acute myocardial infarction

Evidence for altered sensitivity of the nitric oxide/cGMP signalling cascade in insulin-resistant skeletal muscle

Role of hyperhomocysteinemia in endothelial dysfunction and atherothrombotic disease

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