Cigarette smoke metal‐catalyzed protein oxidation leads to vascular endothelial cell contraction by depolymerization of microtubules

Bernhard, David; Csordás, Adam; Henderson, Blair; Rossmann, Andrea; Kind, Michaela; Wick, Georg

doi:10.1096/fj.04-3192com

Cited by 114 publications

(101 citation statements)

References 48 publications

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“…IL-6 has gained attention as the key cytokine in regulation of the immune response, which leads to a shift from Treg toward Th17 cells, 29 but because expression of IL-17 and the Treg marker FoxP3 did not significantly differ between rapamycinand vehicle-treated mice of group 2, we concluded that at this time point, IL-6 seems only to be an indicator for the endothelial cell damage, as has been shown before. 30,31 Nevertheless, further studies using cell-specific knockout mice, as has been shown by the group of Quaggin, 19,20 are needed to evaluate the influence of rapamycin on IL-6 and VEGF modulation in anti-GBM GN.…”

Section: Discussionmentioning

confidence: 99%

Differential Effects of Rapamycin in Anti-GBM Glomerulonephritis

Hochegger

Jansky²,

Soleiman³

et al. 2008

Journal of the American Society of Nephrology

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The immunosuppressive mammalian target of rapamycin inhibitor rapamycin is widely used in solidorgan transplantation, but the effect of rapamycin on kidney disease is controversial. This study evaluated the effect of rapamycin in the autologous phase of anti-glomerular basement membrane (anti-GBM) glomerulonephritis. Disease was induced by preimmunizing the animals with rabbit IgG 5 d before administration of rabbit anti-mouse GBM antiserum. When rapamycin was started on the day of immunization (group 1), mice were protected from glomerulonephritis, suggested by a dramatic decrease in albuminuria, influx of inflammatory cells, and Th1-cytokine expression in the kidneys. Activation of T cells and production of autologous mouse anti-rabbit IgG were also significantly reduced in rapamycin-treated animals. In contrast, when rapamycin was started 14 d after immunization (group 2), mice had a significant increase in albuminuria and renal infiltration of inflammatory cells compared with vehicle-treated animals, and there were no differences in T and B cell responses. A significant decrease in vascular endothelial growth factor-A and an increase in IL-6 were detected in kidneys of these rapamycin-treated mice. In conclusion, rapamycin has the potential to significantly reduce the B and T cell responses and thereby protect from glomerulonephritis when administered early in disease. Once disease is established, however, rapamycin seems to worsen glomerulonephritis by disturbing the endothelial cell/vascular endothelial growth factor system in the kidney.

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Section: Discussionmentioning

confidence: 99%

Differential Effects of Rapamycin in Anti-GBM Glomerulonephritis

Hochegger

Jansky²,

Soleiman³

et al. 2008

Journal of the American Society of Nephrology

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“…Cigarette smoke chemicals were reported to lead to adhesion molecule expression on the surface of endothelial cells and induce the release of proatherogenic cytokines, such as interleukin-6 and interleukin-8. 57 These processes, in combination with cigarette smoke-induced increase in the number and activation of platelets, lead to a significant shift toward a prothrombotic and procoagulative state in the vascular wall of smokers. 38 The core of these processes is the activation of the NFkB cascade.…”

Section: In Vitro Studiesmentioning

confidence: 99%

“…61 Several experimental studies demonstrated that, apart from causing vascular endothelial dysfunction, cigarette smoke causes physical damage to the vascular endothelium (Figure). In essence, 2 forms of damage were observed: (1) contraction of endothelial cells, mediated by oxidation and collapse of the tubulin system, which is reversible and may be part of the clinical symptoms of smoking-caused reduction of FMD, 57 and (2) endothelial cell death. In general, all forms of cell death, that is, apoptosis, necrosis, programmed necrosis (necroptosis), and autophagy, were found to be induced by cigarette smoke chemicals.…”

Section: Arterioscler Thromb Vasc Biol March 2014mentioning

confidence: 99%

Smoking and Cardiovascular Disease

Meßner

Bernhard

2014

ATVB

Self Cite

838

329

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Abstract-Smoking represents one of the most important preventable risk factors for the development of atherosclerosis. The present review aims at providing a comprehensive summary of published data from clinical and animal studies, as well as results of basic research on the proatherogenic effect of smoking. Extensive search and review of literature revealed a vast amount of data on the influence of cigarette smoke and its constituents on early atherogenesis, particularly on endothelial cells. Vascular dysfunction induced by smoking is initiated by reduced nitric oxide (NO) bioavailability and further by the increased expression of adhesion molecules and subsequent endothelial dysfunction. Smoking-induced increased adherence of platelets and macrophages provokes the development of a procoagulant and inflammatory environment. After transendothelial migration and activation, macrophages take up oxidized lipoproteins arising from oxidative modifications and transdifferentiate into foam cells. In addition to direct physical damage to endothelial cells, smoking induces tissue remodeling, and prothrombotic processes together with activation of systemic inflammatory signals, all of which contribute to atherogenic vessel wall changes. There are still great gaps in our knowledge about the effects of smoking on cardiovascular disease. However, we know that smoking cessation is the most effective measure for reversing damage that has already occurred and preventing fatal cardiovascular outcomes. Clinical DataEvidence for smoking-induced initial vascular damage and endothelial dysfunction stems from an array of clinical studies analyzing endothelial function using various techniques. 6 As mentioned above, in 1993, Celermajer et al 5 were able to show that continuous smoking impairs FMD of the brachial artery in a dose-dependent manner, shown by the strong association between FMD and pack years smoked. This was also found to be the case with coronary arteries in a study by Zeiher et al. 7 Interestingly, reduction of endothelium-dependent dilatation by smoking was reversible, and significant improvement of FMD 1 year after cessation has been reported. 8 Likewise, a recent study of Amato et al 9 revealed that smoking light cigarettes impairs FMD as much as smoking regular cigarettes, arguing against light cigarettes as a less harmful alternative.Measurement of FMD represents a useful tool to assess the effects of smoking on the vascular wall. Independent of its FMD reducing activity, smoking was shown to induce other proatherogenic alterations in the vascular wall (eg, by deposition of smoke chemicals). The time needed to restore interrupted functions of the vascular endothelium will depend on the specific process that has caused the endothelial damage; some alterations of the endothelial wall may vanish more rapidly than others, without these being reflected by improved FMD.Clinical studies assessing the interrelation of secondhand smoking and FMD reported strong correlations. Secondhand smoking was shown to impair endo...

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“…There are emerging data suggesting that the alteration of metal homeostasis in the human body by cigarette smoking plays a crucial role in the genesis of a number of diseases. We have recently shown that metals in cigarette smoke are essential in the process leading to damage of the vascular endothelium (1). Dysfunction and disruption of the vascular endothelium is the primary event in the genesis of atherosclerosis, which is the leading cause of death in developed countries and accounts for a dramatically increasing number of deaths in developing countries too.…”

Section: Introductionmentioning

confidence: 99%

Metals in cigarette smoke

Bernhard¹,

Rossmann²,

Wick³

2005

IUBMB Life (International Union of Biochemistry and Molecular B

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254

172

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SummaryMetals are vital for a huge number of physiological processes in the human body, but can also destroy health when the concentration is not within the physiologically favourable range. Cigarette smoking interferes with the carefully controlled metal homeostasis of the human body. This review focuses on the consequences of metal delivery to the human body by cigarette smoking and discusses the body's responses. The metal content of tobacco plants, smoke, the circulation, and various organs is discussed. Finally, we link individual cigarette smoke contained metals to the genesis of human diseases. IUBMB Life, 57: 805 -809, 2005

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Cigarette smoke metal‐catalyzed protein oxidation leads to vascular endothelial cell contraction by depolymerization of microtubules

Cited by 114 publications

References 48 publications

Differential Effects of Rapamycin in Anti-GBM Glomerulonephritis

Differential Effects of Rapamycin in Anti-GBM Glomerulonephritis

Smoking and Cardiovascular Disease

Metals in cigarette smoke

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