Hypothermia induced loss of endothelial barrier function is restored after dopamine pre-treatment; role of ERK activation

2006 ◽  
Vol 45 (3) ◽  
pp. e80
Author(s):  
Boris Rudic ◽  
Paul Thomas Brinkkoetter ◽  
Grietje Beck ◽  
Uwe Gottmann ◽  
Claude Braun ◽  
...  
Keyword(s):  
Barrier Function ◽  
Endothelial Barrier ◽  
Endothelial Barrier Function ◽  
Erk Activation ◽  
Pre Treatment

Abstract 73: Bone Morphogenetic Protein Activity Modulates Endothelial Barrier Function

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Thomas Helbing ◽  
Elena Ketterer ◽  
Bianca Engert ◽  
Jennifer Heinke ◽  
Sebastian Grundmann ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Barrier Function ◽  
Endothelial Permeability ◽  
Bmp Signaling ◽  
Endothelial Barrier ◽  
Endothelial Barrier Function

Introduction: Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome, are associated with high morbidity and mortality in patients. During the progression of ALI, the endothelial cell barrier of the pulmonary vasculature becomes compromised, leading to pulmonary edema, a characteristic feature of ALI. It is well-established that EC barrier dysfunction is initiated by cytoskeletal remodeling, which leads to disruption of cell-cell contacts and formation of paracellular gaps, allowing penetration of protein-rich fluid and inflammatory cells. Bone morphogenetic proteins (BMPs) are important players in endothelial dysfunction and inflammation but their effects on endothelial permeability in ALI have not been investigated until now. Methods and Results: As a first approach to assess the role of BMPs in acute lung injury we analysed BMP4 and BMPER expression in an infectious (LPS) and a non-infectious (bleomycin) mouse models of acute lung injury. In both models BMP4 and BMPER protein expression levels were reduced demonstrated by western blots, suggesting that BMPs are involved in progression ALI. To assess the role of BMPs on vascular leakage, a key feature of ALI, BMP activity in mice was inhibited by i.p. administration of LDN193189, a small molecule that blocks BMP signalling. After 3 days Evans blue dye (EVB) was administered i.v. and dye extravasation into the lungs was quantified as a marker for vascular leakage. Interestingly, LDN193189 significantly increased endothelial permeability compared to control lungs, indicating that BMP signaling is involved in maintenance of endothelial barrier function. To quantify effects of BMP inhibition on endothelial barrier function in vitro, HUVECs were seeded onto transwell filters and were exposed to LDN193189. After 3 days FITC-dextrane was added and passage into the lower chamber was quantified as a marker for endothelial barrier function. Thrombin served as a positive control. As expected from our in vivo experiments inhibition of BMP signaling by LDN193189 enhanced FITC-dextrane passage. To study specific effects of BMPs on endothelial barrier function, two protagonist of the BMP family, BMP2 and BMP4, or BMP modulator BMPER were tested in the transwell assay in vitro. Interestingly BMP4 and BMPER, but not BMP2, reduced FITC-dextrane passage demonstrating that BMP4 and BMPER improved endothelial barrier function. Vice versa, specific knock down of BMP4 or BMPER increased leakage in transwell assays. Im immuncytochemistry silencing of BMPER or BMP4 induced hyperpermeability as a consequence of a pro-inflammatory endothelial phenotype characterised by reduced cell-cell contacts and increased actin stress fiber formation. Additionally, the pro-inflammatory endothelial phenotype was confirmed by real-time revealing increased expression of adhesion molecules ICAM-1 or proinflammatory cytokines such as IL-6 and IL-8 in endothelial cells after BMPER or BMP4 knock down. Confirming these in vitro results BMPER +/- mice exhibit increased extravasation of EVB into the lungs, indicating that partial loss of BMPER impairs endothelial barrier function in vitro and in vivo. Conclusion: We identify BMPER and BMP4 as local regulators of vascular permeability. Both are protective for endothelial barrier function and may open new therapeutic avenues in the treatment of acute lung injury.

Role of Protein Kinase C Isoforms in Rat Epididymal Microvascular Endothelial Barrier Function

2003 ◽  
Vol 28 (5) ◽  
pp. 626-636 ◽  
Author(s):  
Elizabeth O. Harrington ◽  
Jodi L. Brunelle ◽  
Christopher J. Shannon ◽  
Eric S. Kim ◽  
Kirstin Mennella ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Barrier Function ◽  
Endothelial Barrier ◽  
Endothelial Barrier Function ◽  
Kinase C ◽  
Microvascular Endothelial ◽  
Protein Kinase C Isoforms

Hypothermia-Induced Loss of Endothelial Barrier Function Is Restored after Dopamine Pretreatment: Role of p42/p44 Activation

2006 ◽  
Vol 82 (4) ◽  
pp. 534-542 ◽  
Author(s):  
Paul-Thomas Brinkkoetter ◽  
Grietje C. Beck ◽  
Uwe Gottmann ◽  
Ralf Loesel ◽  
Ulf Schnetzke ◽  
...  
Keyword(s):  
Barrier Function ◽  
Endothelial Barrier ◽  
Endothelial Barrier Function

scholarly journals Role of Calcium Signaling in Endothelial Barrier Function

2014 ◽  
Vol 106 (2) ◽  
pp. 719a-720a
Author(s):  
Judith A. Stolwijk ◽  
Christian W. Renken ◽  
Mohamed Trebak
Keyword(s):  
Calcium Signaling ◽  
Barrier Function ◽  
Endothelial Barrier ◽  
Endothelial Barrier Function

Glucosylation of small GTP-binding Rho proteins disrupts endothelial barrier function

1997 ◽  
Vol 272 (1) ◽  
pp. L38-L43 ◽  
Author(s):  
S. Hippenstiel ◽  
S. Tannert-Otto ◽  
N. Vollrath ◽  
M. Krull ◽  
I. Just ◽  
...  
Keyword(s):  
Barrier Function ◽  
Endothelial Permeability ◽  
Endothelial Barrier ◽  
Dependent Manner ◽  
Rho Proteins ◽  
Filamentous Actin ◽  
Endothelial Barrier Function ◽  
Gtp Binding ◽  
Escherichia Coli Hemolysin

The endothelial cytoskeleton is important for the regulation of endothelial barrier function. Small GTP-binding Rho proteins play a central role in the organization of the microfilament system. Clostridium difficile toxin B (TcdB) inactivates Rho proteins by glucosylation at Thr-37. We used TcdB as a probe to study the role of Rho proteins in the regulation of endothelial barrier function. TcdB time (50-170 min) and dose (10-100 ng/ml) dependently increased the hydraulic conductivity of cultured porcine pulmonary artery endothelial cell monolayers approximately 10-fold. Simultaneously, the albumin reflection coefficient decreased substantially from 0.8 to 0.15. Before endothelial hyperpermeability, TcdB reduced F-actin content in a dose-dependent manner, whereas G-actin content remained unchanged. Finally, we proved that TcdB caused dose (5-100 ng/ml)- and time-dependent glucosylation of Rho proteins in endothelial cells. Phalloidin, which stabilizes filamentous actin, prevented the effect of TcdB on endothelial permeability. In contrast to thrombin-, hydrogen peroxide-, or Escherichia coli hemolysin-induced hyperpermeability, the elevation of cyclic nucleotides did not block TcdB-related permeability. The data demonstrate a central role of small GTP-binding Rho proteins for the control of endothelial barrier function.

scholarly journals The role of sphingolipids in endothelial barrier function

2015 ◽  
Vol 396 (6-7) ◽  
pp. 681-691 ◽  
Author(s):  
Peter L. Jernigan ◽  
Amy T. Makley ◽  
Richard S. Hoehn ◽  
Michael J. Edwards ◽  
Timothy A. Pritts
Keyword(s):  
Barrier Function ◽  
Biologically Active ◽  
Endothelial Barrier ◽  
Endothelial Barrier Function ◽  
Physiologic Function ◽  
Sphingosine 1 Phosphate ◽  
Endothelial Integrity ◽  
Pathologic Processes ◽  
Immense Potential

Abstract Sphingolipids are a ubiquitous family of essential lipids with an increasingly understood role as biologically active mediators in numerous physiologic and pathologic processes. Two particular sphingolipid species, sphingosine-1-phosphate and ceramide, and their metabolites interact both directly and indirectly with endothelial cells to regulate vascular permeability. Sphingosine-1-phosphate generally augments endothelial integrity while ceramide tends to promote vascular leak, and a tight balance between the two is necessary to maintain normal physiologic function. The mechanisms by which sphingolipids regulate endothelial barrier function are complex and occur through multiple different pathways, and disruptions or imbalances in these pathways have been implicated in a number of specific disease processes. With improved understanding of sphingolipid biology, endothelial function, and the interactions between the two, several targets for therapeutic intervention have emerged and there is immense potential for further advancement in this field.

Interactions between Epac1 and ezrin in the control of endothelial barrier function

2014 ◽  
Vol 42 (2) ◽  
pp. 274-278 ◽  
Author(s):  
Euan Parnell ◽  
Stephen J. Yarwood
Keyword(s):  
Cardiovascular Disease ◽  
Endothelial Dysfunction ◽  
Barrier Function ◽  
Endothelial Barrier ◽  
Endothelial Barrier Function ◽  
Growing Body ◽  
Cytoskeletal Dynamics ◽  
Inflammatory Signalling ◽  
Kinase A

Loss of barrier function in the vasculature promotes inflammatory signalling which in turn contributes to the progression of cardiovascular disease. cAMP can protect against endothelial dysfunction through the effectors PKA (protein kinase A) and Epac (exchange protein directly activated by cAMP). The present review outlines the role of Epac1 signalling within the endothelium and, in particular, the role of Epac1 in cytoskeletal dynamics and the control of cell morphology. The actin/cytoskeleton linker ezrin will be described in terms of the growing body of evidence placing it downstream of cAMP signalling as a mediator of altered cellular morphology.

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