scholarly journals Regulation of endothelial barrier function by TGF-β type I receptor ALK5: Potential role of contractile mechanisms and heat shock protein 90

2011 ◽  
Vol 227 (2) ◽  
pp. 759-771 ◽  
Author(s):  
Alexander S. Antonov ◽  
Galina N. Antonova ◽  
Makiko Fujii ◽  
Peter ten Dijke ◽  
Vaishali Handa ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Barrier Function ◽  
Potential Role ◽  
Heat Shock Protein 90 ◽  
Endothelial Barrier ◽  
Type I ◽  
Endothelial Barrier Function

scholarly journals Heat Shock Protein 90 Inhibitors Protect and Restore Pulmonary Endothelial Barrier Function

2008 ◽  
Vol 39 (5) ◽  
pp. 551-559 ◽  
Author(s):  
Alexander Antonov ◽  
Connie Snead ◽  
Boris Gorshkov ◽  
Galina N. Antonova ◽  
Alexander D. Verin ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Barrier Function ◽  
Heat Shock Protein 90 ◽  
Endothelial Barrier ◽  
Endothelial Barrier Function

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.

scholarly journals Heat Shock Protein 90 as Therapeutic Target for CVDs and Heart Ageing

2022 ◽  
Vol 23 (2) ◽  
pp. 649
Author(s):  
Siarhei A. Dabravolski ◽  
Vasily N. Sukhorukov ◽  
Vladislav A. Kalmykov ◽  
Nikolay A. Orekhov ◽  
Andrey V. Grechko ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Molecular Chaperones ◽  
Heat Shock Protein 90 ◽  
Misfolded Proteins ◽  
Heart Cells ◽  
Metabolic Demand ◽  
Heart Protection ◽  
High Metabolic Demand

Cardiovascular diseases (CVDs) are the leading cause of death globally, representing approximately 32% of all deaths worldwide. Molecular chaperones are involved in heart protection against stresses and age-mediated accumulation of toxic misfolded proteins by regulation of the protein synthesis/degradation balance and refolding of misfolded proteins, thus supporting the high metabolic demand of the heart cells. Heat shock protein 90 (HSP90) is one of the main cardioprotective chaperones, represented by cytosolic HSP90a and HSP90b, mitochondrial TRAP1 and ER-localised Grp94 isoforms. Currently, the main way to study the functional role of HSPs is the application of HSP inhibitors, which could have a different way of action. In this review, we discussed the recently investigated role of HSP90 proteins in cardioprotection, atherosclerosis, CVDs development and the involvements of HSP90 clients in the activation of different molecular pathways and signalling mechanisms, related to heart ageing.

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
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