Elevated Concentration of Soluble Vascular Endothelial Cadherin Is Associated With Coronary Atherosclerosis

Soeki, Takeshi; Tamura, Yoshiyuki; Shinohara, Hisanori; Sakabe, Koichi; Onose, Yukiko; Fukuda, Nobuo

doi:10.1253/circj.68.1

Cited by 62 publications

(51 citation statements)

References 31 publications

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“…Reduced VE-cadherin protein content was also detected; a finding that may in part be responsible for the observed intercellular gaps. An increased plasma concentration of VE-cadherin has been associated with coronary atherosclerosis (Soeki et al, 2004), and in vitro studies have shown that hydrogen peroxide induces internalization of VE-cadherin and gap formation (Kevil et al, 1998). Hence, the decreased VE-cadherin may be due to internalization and degradation or release into the cell culture medium.…”

Section: Discussionmentioning

confidence: 99%

Activation of protein kinase C and disruption of endothelial monolayer integrity by sodium arsenite—Potential mechanism in the development of atherosclerosis

Pereira

Coffin

Beall

2007

Toxicology and Applied Pharmacology

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Arsenic exposure has been shown to exacerbate atherosclerosis, beginning with activation of the endothelium that lines the vessel wall. Endothelial barrier integrity is maintained by proteins of the adherens junction (AJ) such as vascular endothelial cadherin (VE-cadherin) and β-catenin and their association with the actin cytoskeleton. In the present study, human aortic endothelial cells (HAECs) were exposed to 1, 5 and 10 μM sodium arsenite [As(III)] for 1, 6, 12 and 24 h, and the effects on endothelial barrier integrity were determined. Immunofluorescence studies revealed formation of actin stress fibers and non-uniform VE-cadherin and β-catenin staining at cell-cell junctions that were concentration and time-dependent. Intercellular gaps were observed with a measured increase in endothelial permeability. In addition, concentration-dependent increases in tyrosine phosphorylation (PY) of β-catenin and activation of protein kinase Cα (PKCα) were observed. Inhibition of PKCα restored VE-cadherin and β-catenin staining at cell-cell junctions and abolished the As(III) induced formation of actin stress fibers and intercellular gaps. Endothelial permeability and PY of β-catenin were also reduced to basal levels. These results demonstrate that As(III) induces activation of PKCα, which leads to increased PY of β-catenin downstream of PKCα activation. Phosphorylation of β-catenin plausibly severs the association of VE-cadherin and β-catenin, which along with formation of actin stress fibers, results in intercellular gap formation and increased endothelial permeability. To the best of our knowledge, this is the first report demonstrating that As(III) causes a loss of endothelial monolayer integrity, which potentially could contribute to the development of atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

Activation of protein kinase C and disruption of endothelial monolayer integrity by sodium arsenite—Potential mechanism in the development of atherosclerosis

Pereira

Coffin

Beall

2007

Toxicology and Applied Pharmacology

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“…There is now increasing evidence from basic, pathological and clinical research that atherosclerosis is an inflammatory disease [5][6][7] initiated by endothelial injury and subsequent dysfunction via deleterious effects of risk factors such as oxidized low-density lipoprotein (LDL), hypertension and hyperglycemia. [5][6][7][8][9] We and others have shown that both the coronary and peripheral artery endothelium is injured and dysfunctional in smokers, [10][11][12][13][14][15][16][17][18] and that the administration of antioxidants improves endothelial dysfunction in both smokers and in vitro experiments, indicating that reactive oxygen species (ROS) are involved in the genesis of the endothelial dysfunction in smokers. [14][15][19][20][21][22] However, what is not well known is whether smoking is associated with inflammation and what is its relationship with other risk factors.…”

mentioning

confidence: 99%

Low-Grade Inflammation, Thrombogenicity, and Atherogenic Lipid Profile in Cigarette Smokers

Yasue

Hirai

Mizuno

et al. 2006

Circ J

102

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“…The authors thus suggested that sVE could be used as a marker of atherosclerosis in atherosclerotic disease rather than an inflammatory marker. 18 Serum sVE levels were significantly increased in HSP patients at the acute stage. This might be an indicator of the overall severity of the disease or the result of an immuno-inflammatory response to factors that damage vessels' endothelium.…”

Section: Can Acute and Chronic Diseases Regulate Sve Expression Diffementioning

confidence: 89%

“…In the Soeki et al study, 18 the authors examined sVE in coronary artery disease because VEC had been shown to be expressed in endothelial cells from atherosclerotic lesions, and was associated with neovascularization. 18 In patients with acute myocardial infarction, plasma sVE concentrations were unchanged in the acute and chronic phases. The authors thus suggested that sVE could be used as a marker of atherosclerosis in atherosclerotic disease rather than an inflammatory marker.…”

Section: Can Acute and Chronic Diseases Regulate Sve Expression Diffementioning

confidence: 99%

Soluble vascular endothelial-cadherin and auto-antibodies to human vascular endothelial-cadherin in human diseases: Two new biomarkers of endothelial dysfunction

2015

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Vascular endothelial-cadherin is the most important transmembrane component of endothelial adherens junctions, exclusively expressed by endothelial cells in all types of vessels. Targeting either the extracellular domain or the cytoplasmic tail deleteriously affects the junctional strength and leads to vascular permeability. Recently, cytokineinduced phosphorylation of the vascular endothelial-cadherin cytoplasmic domain was reported to trigger cleavage of its extracellular domain, producing the soluble form of the protein -soluble vascular endothelial-cadherin. Hence, the presence of soluble vascular endothelial-cadherin or auto-antibodies to human vascular endothelial-cadherin in human serum could signalize the presence of vascular abnormalities. This systematic review covers many human studies reporting increased levels of soluble vascular endothelial-cadherin, as well as auto-antibodies to human vascular endothelial-cadherin, which could be promising biomarkers of endothelial dysfunction in a large panel of diseases.

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Elevated Concentration of Soluble Vascular Endothelial Cadherin Is Associated With Coronary Atherosclerosis

Cited by 62 publications

References 31 publications

Activation of protein kinase C and disruption of endothelial monolayer integrity by sodium arsenite—Potential mechanism in the development of atherosclerosis

Activation of protein kinase C and disruption of endothelial monolayer integrity by sodium arsenite—Potential mechanism in the development of atherosclerosis

Low-Grade Inflammation, Thrombogenicity, and Atherogenic Lipid Profile in Cigarette Smokers

Soluble vascular endothelial-cadherin and auto-antibodies to human vascular endothelial-cadherin in human diseases: Two new biomarkers of endothelial dysfunction

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