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      Angiopoietin-2 Levels as Predictors of Outcome in Mechanically Ventilated Patients with Acute Respiratory Distress Syndrome

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          Abstract

          Pulmonary endothelium dysfunction is a key characteristic of ARDS. The aim of this study was to investigate endothelium-derived markers, such as angiopoietin-2 (Ang-2) and endothelial cell-specific molecule-1 (endocan), at the vascular and alveolar compartments as outcome predictors in ARDS. Fifty-three consecutive ARDS patients were studied. The primary outcome was 28-day mortality. Secondary endpoints were days of unassisted ventilation and days with organ failure other than ARDS, during the 28-day study period. Nonsurvivors presented higher lung injury scores and epithelial lining fluid (ELF) Ang-2 levels compared to survivors, with no significant differences in plasma Ang-2, endocan, and protein C concentrations between the two groups. In logistic regression analysis, ELF Ang-2 levels > 705 pg/ml were the only independent variable for 28-day mortality among the previous four. Plasma endocan values > 13 ng/pg were the only parameter predictive against days of unassisted ventilation during the 28-day study period. Finally, lung injury score > 2.25 and ELF Ang-2 levels > 705 pg/ml were associated with increased number of days with organ failure, other than ARDS. Our findings suggest that Ang-2 levels are increased in the alveolar compartment of ARDS patients, and this may be associated both with increased mortality and organ failure besides lung.

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          Most cited references22

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          Immunothrombosis in Acute Respiratory Distress Syndrome: Cross Talks between Inflammation and Coagulation.

          Acute respiratory distress syndrome (ARDS) is defined as a syndrome of acute onset, with bilateral opacities on chest imaging and respiratory failure not caused by cardiac failure, leading to mild, moderate, or severe oxygenation impairment. The syndrome is most commonly a manifestation of sepsis-induced organ dysfunction, characterized by disruption of endothelial barrier integrity and diffuse lung damage. Imbalance between coagulation and inflammation is a predominant characteristic of ARDS, leading to extreme inflammatory response and diffuse fibrin deposition in vascular capillary bed and alveoli. Activated platelets, neutrophils, endothelial cells, neutrophil extracellular traps, microparticles, and coagulation proteases, participate in the complex process of immunothrombosis, which is a key event in ARDS pathophysiology. The present review is focused on the elucidation of immunothrombosis in ARDS and the potential therapeutic implications.
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            Endocan or endothelial cell specific molecule-1 (ESM-1): a potential novel endothelial cell marker and a new target for cancer therapy.

            Endocan, previously called endothelial cell specific molecule-1, is a soluble proteoglycan of 50 kDa, constituted of a mature polypeptide of 165 amino acids and a single dermatan sulphate chain covalently linked to the serine residue at position 137. This dermatan sulphate proteoglycan, which is expressed by the vascular endothelium, has been found freely circulating in the bloodstream of healthy subjects. Experimental evidence is accumulating that implicates endocan as a key player in the regulation of major processes such as cell adhesion, in inflammatory disorders and tumor progression. Inflammatory cytokines such as TNF-alpha, and pro-angiogenic growth factors such as VEGF, FGF-2 and HGF/SF, strongly increased the expression, synthesis or the secretion of endocan by human endothelial cells. Endocan is clearly overexpressed in human tumors, with elevated serum levels being observed in late-stage lung cancer patients, as measured by enzyme-linked immunoassay, and with its overexpression in experimental tumors being evident by immunohistochemistry. Recently, the mRNA levels of endocan have also been recognized as being one of the most significant molecular signatures of a bad prognosis in several types of cancer including lung cancer. Overexpression of this dermatan sulphate proteoglycan has also been shown to be directly involved in tumor progression as observed in mouse models of human tumor xenografts. Collectively, these results suggest that endocan could be a biomarker for both inflammatory disorders and tumor progression as well as a validated therapeutic target in cancer. On the basis of the recent successes of immunotherapeutic approaches in cancer, the preclinical data on endocan suggests that an antibody raised against the protein core of endocan could be a promising cancer therapy.
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              The pulmonary endothelium in acute respiratory distress syndrome: insights and therapeutic opportunities.

              The pulmonary endothelium is a dynamic, metabolically active layer of squamous endothelial cells ideally placed to mediate key processes involved in lung homoeostasis. Many of these are disrupted in acute respiratory distress syndrome (ARDS), a syndrome with appreciable mortality and no effective pharmacotherapy. In this review, we consider the role of the pulmonary endothelium as a key modulator and orchestrator of ARDS, highlighting advances in our understanding of endothelial pathobiology and their implications for the development of endothelial-targeted therapeutics including cell-based therapies. We also discuss mechanisms to facilitate the translation of preclinical data into effective therapies including the application of biomarkers to phenotype patients with ARDS with a predominance of endothelial injury and emerging biotechnologies that could enhance delivery, discovery and testing of lung endothelial-specific therapeutics.
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                Author and article information

                Journal
                Dis Markers
                Dis. Markers
                DM
                Disease Markers
                Hindawi
                0278-0240
                1875-8630
                2017
                29 August 2017
                : 2017
                : 6758721
                Affiliations
                1Second Department of Critical Care Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece
                2Laboratory of Hematology & Blood Bank Unit, Medical School, National and Kapodistrian University of Athens, Athens, Greece
                34th Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece
                4Department of Biochemistry, Athens University Hospital Attikon, Medical School, National and Kapodistrian University of Athens, Athens, Greece
                Author notes
                *Iraklis Tsangaris: itsagkaris@ 123456med.uoa.gr

                Academic Editor: Michael Hawkes

                Author information
                http://orcid.org/0000-0003-4395-0471
                http://orcid.org/0000-0002-7682-4482
                http://orcid.org/0000-0001-8927-9631
                http://orcid.org/0000-0002-1635-7309
                http://orcid.org/0000-0003-4713-3911
                Article
                10.1155/2017/6758721
                5602490
                28947844
                bcb8e8bd-6170-479f-8b86-207ffe057dea
                Copyright © 2017 Iraklis Tsangaris et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 16 February 2017
                : 6 June 2017
                : 4 July 2017
                Categories
                Research Article

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