Leukocytes talking to VE-cadherin

Ley, Klaus

doi:10.1182/blood-2013-08-519918

Cited by 7 publications

(5 citation statements)

References 12 publications

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“…Whether α-2, 6 sialylation regulates interactions between monocytes and endothelial cells remains unknown. Endothelial tight junctions have been studied extensively53637. VE-Cadherin, an important target protein, contributes to the maintenance of vascular integrity and promotes endothelial cell-to-cell adhesion28.…”

Section: Discussionmentioning

confidence: 99%

TNF-α regulates the proteolytic degradation of ST6Gal-1 and endothelial cell-cell junctions through upregulating expression of BACE1

Deng

Zhang

Liu

et al. 2017

Sci Rep

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Endothelial dysfunction and monocyte adhesion to vascular endothelial cells are two critical steps in atherosclerosis development, and emerging evidence suggests that protein sialylation is involved in these processes. However, the mechanism underlying this phenomenon remains incompletely elucidated. In this study, we demonstrated that treatment with the proinflammatory cytokine TNF-α disrupted vascular endothelial cell-cell tight junctions and promoted monocyte endothelial cell adhesion. Western blotting and Sambucus nigra lectin (SNA) blotting analyses revealed that TNF-α treatment decreased α-2, 6-sialic acid transferase 1 (ST6Gal-I) levels and downregulated VE-Cadherin α-2, 6 sialylation. Further analysis demonstrated that TNF-α treatment upregulated β-site amyloid precursor protein enzyme 1 (BACE1) expression, thus resulting in sequential ST6Gal-I proteolytic degradation. Furthermore, our results revealed that PKC signaling cascades were involved in TNF-α-induced BACE1 upregulation. Together, these results indicated that the proinflammatory cytokine TNF-α impairs endothelial tight junctions and promotes monocyte-endothelial cell adhesion by upregulating BACE1 expression through activating PKC signaling and sequentially cleaving ST6Gal-I. Thus, inhibition of BACE1 expression may be a new approach for treating atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

TNF-α regulates the proteolytic degradation of ST6Gal-1 and endothelial cell-cell junctions through upregulating expression of BACE1

Deng

Zhang

Liu

et al. 2017

Sci Rep

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“…In fact, recent in vitro studies have shown a direct positive correlation between VE-cadherin expression and oxidative stress [ 48 ] suggesting this being part of a cytoprotective response mechanism. In fact, VE-cadherin acts as a master regulator of various endothelial functions including modulation of cell-cell adhesion, angiogenesis, and vascular permeability to leukocytes in response to VCAM-1 activation [ 49 ], whose expression level was also increased (see Figure 6 ). Note also that an up-regulation of claudin-5 (in this case mediated by VE-cadherin) does not necessarily translate into an improved BBB integrity.…”

Section: Discussionmentioning

confidence: 99%

Oxidative and pro-inflammatory impact of regular and denicotinized cigarettes on blood brain barrier endothelial cells: is smoking reduced or nicotine-free products really safe?

et al. 2014

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BackgroundBoth active and passive tobacco smoke (TS) potentially impair the vascular endothelial function in a causative and dose-dependent manner, largely related to the content of reactive oxygen species (ROS), nicotine, and pro-inflammatory activity. Together these factors can compromise the restrictive properties of the blood–brain barrier (BBB) and trigger the pathogenesis/progression of several neurological disorders including silent cerebral infarction, stroke, multiple sclerosis and Alzheimer’s disease. Based on these premises, we analyzed and assessed the toxic impact of smoke extract from a range of tobacco products (with varying levels of nicotine) on brain microvascular endothelial cell line (hCMEC/D3), a well characterized human BBB model.ResultsInitial profiling of TS showed a significant release of reactive oxygen (ROS) and reactive nitrogen species (RNS) in full flavor, nicotine-free (NF, “reduced-exposure” brand) and ultralow nicotine products. This release correlated with increased oxidative cell damage. In parallel, membrane expression of endothelial tight junction proteins ZO-1 and occludin were significantly down-regulated suggesting the impairment of barrier function. Expression of VE-cadherin and claudin-5 were also increased by the ultralow or nicotine free tobacco smoke extract. TS extract from these cigarettes also induced an inflammatory response in BBB ECs as demonstrated by increased IL-6 and MMP-2 levels and up-regulation of vascular adhesion molecules, such as VCAM-1 and PECAM-1.ConclusionsIn summary, our results indicate that NF and ultralow nicotine cigarettes are potentially more harmful to the BBB endothelium than regular tobacco products. In addition, this study demonstrates that the TS-induced toxicity at BBB ECs is strongly correlated to the TAR and NO levels in the cigarettes rather than the nicotine content.

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“…There are three types of transmembrane molecules at endothelial tight junction that form the endothelial barrier including occludin, claudins, and JAMs (64,74). The important gatekeeper in modulating the transmigration of leukocyte is VE-cadherin (vascular endothelial-cadherin, CD144) and PECAM-1 (75)(76)(77). JAMs, VE-cadherin and PECAM-1 would regulate the passage of leukocyte by inducing cytoskeletal remodeling leading to changes in the integrity of endothelial junction (Table 1) (76,(78)(79)(80).…”

Section: Leukocyte Recruitmentmentioning

confidence: 99%

Platelet adhesion on endothelium early after vein grafting mediates leukocyte recruitment and intimal hyperplasia in a murine model

Tseng¹,

Chang²,

Lengquist³

et al. 2015

Thromb Haemost

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Intimal hyperplasia (IH) is the substrate for accelerated atherosclerosis and limited patency of vein grafts. However, there is still no specific treatment targeting IH following graft surgery. In this study, we used a mouse model of vein grafting to investigate the potential for early intervention with platelet function for later development of graft IH. We transferred the inferior vena cava (IVC) from donor C57BL/6 mice to the carotid artery in recipients using a cuff technique. We found extensive endothelial injury and platelet adhesion one hour following grafting. Adhesion of leukocytes was distinct in areas of platelet adhesion. Platelet and leukocyte adhesion was strongly reduced in mice receiving a function-blocking antibody against the integrin αIIbβ3. This was followed by a reduction of IH one month following grafting. Depletion of platelets using antiserum also reduced IH at later time points. These findings indicate platelets as pivotal to leukocyte recruitment to the wall of vein grafts. In conclusion, the data also highlight early intervention of platelets and inflammation as potential treatment for later formation of IH and accelerated atherosclerosis following bypass surgery.

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Leukocytes talking to VE-cadherin

Cited by 7 publications

References 12 publications

TNF-α regulates the proteolytic degradation of ST6Gal-1 and endothelial cell-cell junctions through upregulating expression of BACE1

TNF-α regulates the proteolytic degradation of ST6Gal-1 and endothelial cell-cell junctions through upregulating expression of BACE1

Oxidative and pro-inflammatory impact of regular and denicotinized cigarettes on blood brain barrier endothelial cells: is smoking reduced or nicotine-free products really safe?

Platelet adhesion on endothelium early after vein grafting mediates leukocyte recruitment and intimal hyperplasia in a murine model

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