VE-Cadherin

Vestweber, Dietmar

doi:10.1161/atvbaha.107.158014

Cited by 675 publications

(307 citation statements)

References 112 publications

(113 reference statements)

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“…Interestingly, this effect was mediated by enhanced intercellular junctions resembling a protective mechanism previously reported in brain endothelial cells where active vitamin D preserved the barrier integrity following hypoxia 36. Here, we found that paricalcitol strengthened the adherens junction protein VE‐cadherin in HUVECs, an endothelium‐specific homotypic adhesion protein essential to control the integrity of the endothelial monolayer 29. In addition, VE‐cadherin interacts, via other proteins, with the F‐actin cytoskeleton to orchestrate the cell‐cell contact and thus maintaining barrier function 37.…”

Section: Discussionsupporting

confidence: 83%

“…No significant impact on the basal endothelial barrier function was detected 24 hours after the addition of α‐Klotho (400 pM; 4.3%), nor for the lower dose of paricalcitol (10 nmol/L; 5.3%) when compared with control (Figure 4A). Based on our current findings, we proceeded by evaluating whether the distribution of the main adherens junction protein VE‐cadherin, a determinant of endothelial junctional stability,29 and F‐actin rearrangement could explain the changes of endothelial barrier enhancements. Immunostaining for VE‐cadherin revealed that paricalcitol significantly enhanced its peripheral localization in a dose‐dependent manner (39% for 10 nmol/L and 48% for 100 nmol/L) compared with control conditions (Figure 4B and 4C).…”

Section: Resultsmentioning

confidence: 99%

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Vitamin D Attenuates Endothelial Dysfunction in Uremic Rats and Maintains Human Endothelial Stability

Cuenca

Ferrantelli

Meinster

et al. 2018

JAHA

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BackgroundDysfunctional endothelium may contribute to the development of cardiovascular complications in chronic kidney disease (CKD). Supplementation with active vitamin D has been proposed to have vasoprotective potential in CKD, not only by direct effects on the endothelium but also by an increment of α‐Klotho. Here, we explored the capacity of the active vitamin D analogue paricalcitol to protect against uremia‐induced endothelial damage and the extent to which this was dependent on increased α‐Klotho concentrations.Methods and ResultsIn a combined rat model of CKD with vitamin D deficiency, renal failure induced vascular permeability and endothelial‐gap formation in thoracic aorta irrespective of baseline vitamin D, and this was attenuated by paricalcitol. Downregulation of renal and serum α‐Klotho was found in the CKD model, which was not restored by paricalcitol. By measuring the real‐time changes of the human endothelial barrier function, we found that paricalcitol effectively improved the recovery of endothelial integrity following the addition of the pro‐permeability factor thrombin and the induction of a wound. Furthermore, immunofluorescence staining revealed that paricalcitol promoted vascular endothelial‐cadherin–based cell‐cell junctions and diminished F‐actin stress fiber organization, preventing the formation of endothelial intracellular gaps.ConclusionsOur results demonstrate that paricalcitol attenuates the CKD‐induced endothelial damage in the thoracic aorta and directly mediates endothelial stability in vitro by enforcing cell‐cell interactions.

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Section: Discussionsupporting

confidence: 83%

Section: Resultsmentioning

confidence: 99%

Vitamin D Attenuates Endothelial Dysfunction in Uremic Rats and Maintains Human Endothelial Stability

Cuenca

Ferrantelli

Meinster

et al. 2018

JAHA

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“…Presence of endothelial-specific adhesion molecule, vascular endothelial cadherin (VE-cadherin), which is exclusively expressed and located at the basal side of the EC contacts, 6,11 is an essential step that indicates the extent of permeability of blood vessels through the paracellular pathway. 11 Clathrin-, lipid raft-, or caveolae-mediated endocytosis is considered as means of transcellular transport.…”

Section: Introductionmentioning

confidence: 99%

“…11 Clathrin-, lipid raft-, or caveolae-mediated endocytosis is considered as means of transcellular transport. 12 In intestinal cells, endocytosis involves clathrin-coated pits that internalize cargo and deliver it to other cellular destinations.…”

Section: Introductionmentioning

confidence: 99%

Ablation of MMP9 Gene Ameliorates Paracellular Permeability and Fibrinogen–Amyloid Beta Complex Formation during Hyperhomocysteinemia

Muradashvili

Tyagi

Metreveli

et al. 2014

J Cereb Blood Flow Metab

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Increased blood level of homocysteine (Hcy), called hyperhomocysteinemia (HHcy) accompanies many cognitive disorders including Alzheimer's disease. We hypothesized that HHcy-enhanced cerebrovascular permeability occurs via activation of matrix metalloproteinase-9 (MMP9) and leads to an increased formation of fibrinogen-b-amyloid (Fg-Ab) complex. Cerebrovascular permeability changes were assessed in C57BL/6J (wild type, WT), cystathionine-b-synthase heterozygote (Cbs þ / À , a genetic model of HHcy), MMP9 gene knockout (Mmp9 À / À ), and Cbs and Mmp9 double knockout (Cbs þ / À /Mmp9 À / À ) mice using a dual-tracer probing method. Expression of vascular endothelial cadherin (VE-cadherin) and Fg-Ab complex formation was assessed in mouse brain cryosections by immunohistochemistry. Short-term memory of mice was assessed with a novel object recognition test. The cerebrovascular permeability in Cbs þ / À mice was increased via mainly the paracellular transport pathway. VE-cadherin expression was the lowest and Fg-Ab complex formation was the highest along with the diminished short-term memory in Cbs þ / À mice. These effects of HHcy were ameliorated in Cbs þ / À /Mmp9 À / À mice. Thus, HHcy causes activation of MMP9 increasing cerebrovascular permeability by downregulation of VE-cadherin resulting in an enhanced formation of Fg-Ab complex that can be associated with loss of memory. These data may lead to the identification of new targets for therapeutic intervention that can modulate HHcy-induced cerebrovascular permeability and resultant pathologies.

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“…Movement of substances via the paracellular pathway occurs between the ECs and involves alterations in tight, gap, and adherence junction proteins (Mehta and Malik, 2006). Vascular endothelial cadherin (VE-cadherin), which is a strictly endothelial-specific adhesion molecule, is located at the basal side of the ECs (Mehta and Malik, 2006;Vestweber, 2008). Its presence at cell contacts is an essential step that indicates the extent of permeability of blood vessels through the paracellular pathway (Vestweber, 2008).…”

Section: Introductionmentioning

confidence: 99%

Fibrinogen-Induced Increased Pial Venular Permeability in Mice

Muradashvili

Qipshidze

Munjal

et al. 2011

J Cereb Blood Flow Metab

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Elevated blood level of Fibrinogen (Fg) is commonly associated with vascular dysfunction. We tested the hypothesis that at pathologically high levels, Fg increases cerebrovascular permeability by activating matrix metalloproteinases (MMPs). Fibrinogen (4 mg/mL blood concentration) or equal volume of phosphate-buffered saline (PBS) was infused into male wild-type (WT; C57BL/6J) or MMP-9 gene knockout (MMP9À/À) mice. Pial venular leakage of fluorescein isothiocyanate-bovine serum albumin to Fg or PBS alone and to topically applied histamine (10 À5 mol/L) were assessed. Intravital fluorescence microscopy and image analysis were used to assess cerebrovascular protein leakage. Pial venular macromolecular leakage increased more after Fg infusion than after infusion of PBS in both (WT and MMP9À/À) mice but was more pronounced in WT compared with MMP9À/À mice. Expression of vascular endothelial cadherin (VE-cadherin) was less and plasmalemmal vesicle-associated protein-1 (PV-1) was greater in Fg-infused than in PBS-infused both mice groups. However, in MMP9À/À mice, VE-cadherin expression was greater and PV-1 expression was less than in WT mice. These data indicate that at higher levels, Fg compromises microvascular integrity through activation of MMP-9 and downregulation of VE-cadherin and upregulation of PV-1. Our results suggest that elevated blood level of Fg could have a significant role in cerebrovascular dysfunction and remodeling.

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VE-Cadherin

Cited by 675 publications

References 112 publications

Vitamin D Attenuates Endothelial Dysfunction in Uremic Rats and Maintains Human Endothelial Stability

Vitamin D Attenuates Endothelial Dysfunction in Uremic Rats and Maintains Human Endothelial Stability

Ablation of MMP9 Gene Ameliorates Paracellular Permeability and Fibrinogen–Amyloid Beta Complex Formation during Hyperhomocysteinemia

Fibrinogen-Induced Increased Pial Venular Permeability in Mice

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