Cyanate Is a Novel Inducer of Endothelial ICAM-1 Expression

El‐Gamal, Dalia; Holzer, Michael; Gauster, Martin; Schicho, Rudolf; Binder, Veronika; Kónya, Viktória; Wadsack, Christian; Schuligoi, Rufina; Heinemann, Ákos; Marsche, Gunther

doi:10.1089/ars.2011.4090

Cited by 29 publications

(42 citation statements)

References 40 publications

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“…A significant reduction in migration of the cyanate‐treated endothelial cells was observed, as was impairment of both proliferation and tube formation. This result is consistent with recent data showing that cyanate itself amplifies vascular inflammation . Our in vitro study suggested that cyanate impaired angiogenesis by at least 2 mechanisms: (1) direct effects on endothelial cells, and (2) indirect effects by promoting protein carbamylation.…”

Section: Discussionsupporting

confidence: 93%

“…Consequently, the impaired tissue perfusion induced by cyanate might be mediated in part by the attenuation of endothelial angiogenic function. Similarly, recent studies have demonstrated endothelial dysfunction and reduced endothelial nitric oxide synthase in cyanate‐treated mice . Our results, combined with others, suggest that exposure to cyanate in vivo could impair endothelial function.…”

Section: Discussionsupporting

confidence: 89%

“…[13][14][15] Carbamylated modification of high-density lipoprotein also impairs its endothelial repair properties. 16 In addition to promoting carbamylation, recent studies have demonstrated that cyanate itself can directly induce endothelial dysfunction and adhesion molecule expression 17,18 ; thus, cyanate could serve as a potential regulator of endothelial function. Nonetheless, the effect of cyanate on endothelial angiogenesis properties remains unclear.…”

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confidence: 99%

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Cyanate‐Impaired Angiogenesis: Association With Poor Coronary Collateral Growth in Patients With Stable Angina and Chronic Total Occlusion

Sun

Yang

Mao

et al. 2016

JAHA

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BackgroundCyanate has recently gained attention for its role in the pathogenesis of vascular injury. Nonetheless, the effect of cyanate on angiogenesis remains unclear.Methods and ResultsIn this study, we demonstrated that oral administration of cyanate impaired blood perfusion recovery in a mouse hind‐limb ischemia model. A reduction in blood perfusion recovery at day 21 was observed in the ischemic tissue of cyanate‐treated mice. Likewise, there were fewer capillaries in the ischemic hind‐limb tissue of cyanate‐exposed mice. Our in vitro study showed that cyanate, together with its carbamylated products, inhibited the migration, proliferation, and tube‐formation abilities of endothelial cells. Further research revealed that cyanate regulated angiogenesis partly by interrupting the vascular endothelial growth factor receptor 2/phosphatidylinositol 3‐kinase/Akt pathway. The serum concentrations of homocitrulline, a marker of cyanate exposure, were determined in 117 patients with stable angina and chronic total occlusion. Consistent with the antiangiogenic role of cyanate, homocitrulline levels were increased in patients with poor coronary collateralization (n=58) compared with those with high collateralization (n=59; 21.09±13.08 versus 15.54±9.02 ng/mL, P=0.009). In addition, elevated homocitrulline concentration was a strong predictor of poor coronary collateral growth.ConclusionsImpaired angiogenesis induced by cyanate might contribute to poor coronary collateral growth.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 89%

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confidence: 99%

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Cyanate‐Impaired Angiogenesis: Association With Poor Coronary Collateral Growth in Patients With Stable Angina and Chronic Total Occlusion

Sun

Yang

Mao

et al. 2016

JAHA

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“…24,48 Carbamylation of high-density lipoprotein (HDL) similarly appears to confer atherogenic properties, 74 and there are studies suggesting that cyanate itself has direct pathologic effects on endothelial cells. 75,76 Most recently, epidemiologic studies have further established protein carbamylation as an independent risk factor for all-cause mortality and death from cardiac causes in both uremic and non-uremic populations (see Figure 2 and Recent Advances). 2,62,77 …”

Section: Pathogenesismentioning

confidence: 99%

Protein Carbamylation in Kidney Disease: Pathogenesis and Clinical Implications

Kalim

Karumanchi

Thadhani

et al. 2014

American Journal of Kidney Diseases

104

101

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Carbamylation describes a non-enzymatic, posttranslational protein modification mediated by cyanate, a dissociation product of urea. When kidney function declines and urea accumulates, the burden of carbamylation naturally rises. Free amino acids may protect proteins from carbamylation, and protein carbamylation has been shown to increase in uremic patients with amino acid deficiencies. Carbamylation reactions are capable of altering the structure and functional properties of certain proteins, and have been directly implicated in the underlying mechanisms of various disease conditions. A broad range of studies has demonstrated how the irreversible binding of urea-derived cyanate to proteins in the human body causes inappropriate cellular responses leading to adverse outcomes such as accelerated atherosclerosis and inflammation. Given carbamylation’s relationship to urea and the evidence that it contributes to disease pathogenesis, measurements of carbamylated proteins may serve as useful quantitative biomarkers of time-averaged urea concentrations while also offering risk assessment in patients with kidney disease. Moreover, the link between carbamylated proteins and disease pathophysiology creates an enticing therapeutic target for reducing the rate of carbamylation. This article reviews the biochemistry of the carbamylation reaction, its role in specific diseases, and the potential diagnostic and therapeutic implications of these findings based on recent advances.

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“…Levels of total cholesterol, nonesterifi ed cholesterol, triglycerides, choline-containing phospholipids (Diasys, Holzheim, Germany), sphingomyelin (Cayman Europe, Tallinn, Estonia), and lysophosphatidylcholine (LPC) (Cosmo Bio Co. LTD, Tokyo, Japan) were measured enzymatically ( 15,22 ). Sphingomyelin values were subtracted from total choline-containing phospholipids to quantify phosphatidylcholine.…”

Section: Determination Of Plasma and Hdl-lipid Compositionmentioning

confidence: 99%

Psoriasis alters HDL composition and cholesterol efflux capacity

Holzer

Wolf

Curcic

et al. 2012

Journal of Lipid Research

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145

141

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This article is available online at http://www.jlr.org more than the skin ( 1 ). Traditional cardiovascular risk factors, such as hypertension, dyslipidemia, and obesity, are more frequent in psoriatic patients ( 2-4 ). However, even after adjusting for these risk factors, psoriasis has been shown to be associated with a higher incidence of myocardial infarction, stroke, and cardiovascular mortality ( 3,5,6 ). In moderate to severe psoriasis, a signifi cantly deteriorated lipid profi le was observed compared with healthy controls, with higher values of low-density lipoprotein, triglycerides, and signifi cantly decreased HDL levels ( 7 ).Recent studies clearly demonstrated that infl ammation impairs reverse cholesterol transfer in vivo ( 8, 9 ), providing evidence that infl ammation impairs HDL function. Emerging evidence suggests that assessment of HDL plasma concentrations alone is insuffi cient and indicate that the quality, rather than the mere quantity, of HDL determines its potential benefi cial effects against atherosclerosis ( 10 ). HDL is a complex lipoprotein particle with a broad variety of functions, also exerting atheroprotective activity via effects on the endothelium and by potent antiinfl ammatory capabilities ( 11-13 ). Recent studies have identifi ed HDL-associated proteins to be involved in the regulation of lipid metabolism, complement activation, growth-factor secretion, and proteolysis (14)(15)(16)(17)(18)(19).Functional impairment of HDL may contribute to the increased cardiovascular mortality experienced by psoriatic patients, but the impact of psoriasis on the composition and function of HDL has not been assessed. As qualitative alterations of HDL seem to be linked with increased cardiovascular complications, we hypothesized that HDL from psoriatic patients displays altered protein cargo and lipid composition, thereby rendering HDL dysfunctional.Abstract Psoriasis, a chronic infl ammatory skin disease, has been linked to increased myocardial infarction and stroke. Functional impairment of HDL may contribute to the excess cardiovascular mortality of psoriatic patients. However, data available regarding the impact of psoriasis on HDL composition and function are limited. HDL from psoriasis patients and healthy controls was isolated by ultracentrifugation and shotgun proteomics, and biochemical methods were used to monitor changed HDL composition. We observed a signifi cant reduction in apoA-I levels of HDL from psoriatic patients, whereas levels of apoA-II and proteins involved in acute-phase response, immune response, and endopeptidase/protease inhibition were increased. Psoriatic HDL contained reduced phospholipid and cholesterol. With regard to function, these compositional alterations impaired the ability of psoriatic HDL to promote cholesterol effl ux from macrophages. Importantly, HDLcholesterol effl ux capability negatively correlated with psoriasis area and severity index. We observed that control HDL, as well as psoriatic HDL, inhibited dihydrorhodamine (DHR) oxidation to a similar...

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Cyanate Is a Novel Inducer of Endothelial ICAM-1 Expression

Abstract: Collectively, our data raise the possibility that cyanate amplifies vascular inflammation, linking inflammation, smoking, and uremia.

Cited by 29 publications

References 40 publications

Cyanate‐Impaired Angiogenesis: Association With Poor Coronary Collateral Growth in Patients With Stable Angina and Chronic Total Occlusion

Cyanate‐Impaired Angiogenesis: Association With Poor Coronary Collateral Growth in Patients With Stable Angina and Chronic Total Occlusion

Protein Carbamylation in Kidney Disease: Pathogenesis and Clinical Implications

Psoriasis alters HDL composition and cholesterol efflux capacity

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