Soluble VE-cadherin is involved in endothelial barrier breakdown in systemic inflammation and sepsis

Flemming, Sven; Burkard, Natalie; Renschler, Melanie; Vielmuth, Franziska; Meir, Michael; Schick, Martin Alexander; Wunder, Christian; Germer, Christoph‐Thomas; Spindler, Volker; Waschke, Jens; Schlegel, Nicolas

doi:10.1093/cvr/cvv144

Cited by 95 publications

(133 citation statements)

References 40 publications

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“…ADAM10 is involved in the shedding of dozens of substrates, such as CX3CL1 [40], IL6-receptor (IL-6R) [40–42], TNF- α , and vascular endothelial cadherin (VE-cadherin) [43, 44]. Among these substrates, Notch, CD44, IL-6R, CX3CL1, CXCL16, VEGFR2, and VE-cadherin are of special importance for vascular biology [45].…”

Section: Discussionmentioning

confidence: 99%

Role of MicroRNA-103a Targeting ADAM10 in Abdominal Aortic Aneurysm

Jiao

Yao

Zhang

et al. 2017

BioMed Research International

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MicroRNAs (miRNAs) are deregulated in various vascular ailments including abdominal aortic aneurysm (AAA). MiR-103 is involved in vascular, metabolic, and malignant diseases, but whether it participates in the pathogenesis of AAA remains elusive. ADAM10 plays a vital role in the formation of aneurysm, but whether miRs modulate its activity during AAA formation is totally unknown. In this study, we detected the significantly increased protein expression of ADAM10 in angiotensin II induced murine AAA specimens, while the mRNA expression of ADAM10 was similar between AAA and control, suggesting the posttranscriptional regulation. The ADAM10 specific inhibitor GI254023X dramatically reduced the macrophage infiltration of murine abdominal aorta. Bioinformatic predictions suggest that ADAM10 is the target of miR-103a/107 but the binding site is exclusive. At the cellular level, miR-103a-1 suppressed the protein expression of ADAM10, while antisense miR-103a-1 increased its expression. Particularly, with the progression of murine AAA, the mRNA expression of miR-103a/107 substantially decreased and the protein expression of ADAM10 greatly increased. Together, our data afford the new insight that miR-103a inhibited AAA growth via targeting ADAM10, which might be a promising therapeutic strategy to alleviate AAA.

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Section: Discussionmentioning

confidence: 99%

Role of MicroRNA-103a Targeting ADAM10 in Abdominal Aortic Aneurysm

Jiao

Yao

Zhang

et al. 2017

BioMed Research International

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“…During sepsis, the vascular barrier is one of the key structures in the pathophysiologic cascade. In experimental conditions, incubation of human dermal microvascular EC with tumor necrosis factor-α and bacterial lipopolysaccharide led to endothelial barrier disruption, which correlated with significantly increased VE-cadherin in cell culture supernatants [23]. Moreover, Zhang et al [6] found, in patients with severe sepsis, significantly increased plasma levels of VE-cadherin and a significant difference between soluble VE-cadherin levels in patients who survived severe sepsis (lower levels) and those who died (higher levels).…”

Section: Discussionmentioning

confidence: 99%

Vascular Endothelial Dysfunction during Cardiac Surgery: On-Pump versus Off-Pump Coronary Surgery

et al. 2017

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Background: Cardiac surgery often causes ischemia and development of a systemic inflammatory response syndrome, which impairs vascular barrier function, normally maintained by the endothelial cell line and the endothelial glycocalyx (EG). The EG normally covers and protects healthy endothelial cells throughout the vasculature. The aim of the present study was to assess the disruption of the cellular part of the microvascular barrier by determining parameters of endothelial cell activation known to influence and reflect cell-cell junctional integrity. Particular attention was placed on angiopoietins and their important effects on endothelial gap junctions. Furthermore, comparative measurements were undertaken in patients undergoing on- and off-pump cardiac surgery, the latter group presumably experiencing less ischemic stress. Methods: 30 patients undergoing elective coronary artery bypass surgery were assigned to the conventional coronary artery bypass (CCAB) group (n = 15) or the off-pump coronary artery bypass grafting (OPCAB) group (n = 15). Blood samples were obtained for measuring angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), vascular endothelial (VE)-cadherin, and endocan at various time points. Results: There were significant increases in all measured parameters in both study groups versus the respective basal values. Maximal increases were as follows: Ang-1: CCAB +220%, OPCAB +166%, p < 0.05 each; Ang-2: CCAB +150%, OPCAB +20%, p < 0.05 each; VE-cadherin: CCAB +87%, OPCAB +66%, p < 0.05 each; endocan: CCAB +323%, OPCAB +72%, p < 0.05 each. Conclusion: The present study demonstrates the activation of endothelial cells, shedding of cell-cell contacts and a potential intrinsic counterregulation by Ang-1 and endocan in patients undergoing major cardiac surgery. Quantitatively greater deviations of parameters in the CCAB than in the OPCAB group suggest a relation between the occurrence of ischemia/reperfusion and the extent of endothelial activation.

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“…Inhibition of ADAM10 blocks soluble VE-cadherin production and preserves endothelial barrier integrity upon TNF or LPS stimulation. In septic patients, plasma levels of soluble VE-cadherin correlate with disease severity (172). …”

Section: Endothelial Response To Gcs In Sepsismentioning

confidence: 99%

Endothelial Response to Glucocorticoids in Inflammatory Diseases

et al. 2016

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The endothelium plays a crucial role in inflammation. A balanced control of inflammation requires the action of glucocorticoids (GCs), steroidal hormones with potent cell-specific anti-inflammatory properties. Besides the classic anti-inflammatory effects of GCs on leukocytes, recent studies confirm that endothelial cells also represent an important target for GCs. GCs regulate different aspects of endothelial physiology including expression of adhesion molecules, production of pro-inflammatory cytokines and chemokines, and maintenance of endothelial barrier integrity. However, the regulation of endothelial GC sensitivity remains incompletely understood. In this review, we specifically examine the endothelial response to GCs in various inflammatory diseases ranging from multiple sclerosis, stroke, sepsis, and vasculitis to atherosclerosis. Shedding more light on the cross talk between GCs and endothelium will help to improve existing therapeutic strategies and develop new therapies better tailored to the needs of patients.

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Soluble VE-cadherin is involved in endothelial barrier breakdown in systemic inflammation and sepsis

Cited by 95 publications

References 40 publications

Role of MicroRNA-103a Targeting ADAM10 in Abdominal Aortic Aneurysm

Role of MicroRNA-103a Targeting ADAM10 in Abdominal Aortic Aneurysm

Vascular Endothelial Dysfunction during Cardiac Surgery: On-Pump versus Off-Pump Coronary Surgery

Endothelial Response to Glucocorticoids in Inflammatory Diseases

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