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      Vascular permeability—the essentials

      review-article
      Upsala Journal of Medical Sciences
      Informa Healthcare
      Edema, histamine, junctions, pore, vascular permeability, VEGF

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          Abstract

          The vasculature, composed of vessels of different morphology and function, distributes blood to all tissues and maintains physiological tissue homeostasis. In pathologies, the vasculature is often affected by, and engaged in, the disease process. This may result in excessive formation of new, unstable, and hyperpermeable vessels with poor blood flow, which further promotes hypoxia and disease propagation. Chronic vessel permeability may also facilitate metastatic spread of cancer. Thus, there is a strong incentive to learn more about an important aspect of vessel biology in health and disease: the regulation of vessel permeability. The current review aims to summarize current insights into different mechanisms of vascular permeability, its regulatory factors, and the consequences for disease.

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          Most cited references51

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          Signal transduction by vascular endothelial growth factor receptors.

          VEGFs (vascular endothelial growth factors) control vascular development during embryogenesis and the function of blood vessels and lymphatic vessels in the adult. There are five related mammalian ligands, which act through three receptor tyrosine kinases. Signalling is modulated through neuropilins, which act as VEGF co-receptors. Heparan sulfate and integrins are also important modulators of VEGF signalling. Therapeutic agents that interfere with VEGF signalling have been developed with the aim of decreasing angiogenesis in diseases that involve tissue growth and inflammation, such as cancer. The present review will outline the current understanding and consequent biology of VEGF receptor signalling.
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            Autocrine VEGF signaling is required for vascular homeostasis.

            Vascular endothelial growth factor (VEGF) is essential for developmental and pathological angiogenesis. Here we show that in the absence of any pathological insult, autocrine VEGF is required for the homeostasis of blood vessels in the adult. Genetic deletion of vegf specifically in the endothelial lineage leads to progressive endothelial degeneration and sudden death in 55% of mutant mice by 25 weeks of age. The phenotype is manifested without detectable changes in the total levels of VEGF mRNA or protein, indicating that paracrine VEGF could not compensate for the absence of endothelial VEGF. Furthermore, wild-type, but not VEGF null, endothelial cells showed phosphorylation of VEGFR2 in the absence of exogenous VEGF. Activation of the receptor in wild-type cells was suppressed by small molecule antagonists but not by extracellular blockade of VEGF. These results reveal a cell-autonomous VEGF signaling pathway that holds significance for vascular homeostasis but is dispensable for the angiogenic cascade.
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              Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid.

              Tumor ascites fluids from guinea pigs, hamsters, and mice contain activity that rapidly increases microvascular permeability. Similar activity is also secreted by these tumor cells and a variety of other tumor cell lines in vitro. The permeability-increasing activity purified from either the culture medium or ascites fluid of one tumor, the guinea pig line 10 hepatocarcinoma, is a 34,000- to 42,000-dalton protein distinct from other known permeability factors.
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                Author and article information

                Journal
                Ups J Med Sci
                Ups. J. Med. Sci
                UPS
                Upsala Journal of Medical Sciences
                Informa Healthcare
                0300-9734
                2000-1967
                August 2015
                31 August 2015
                : 120
                : 3
                : 135-143
                Affiliations
                Uppsala University, Department of Immunology, Genetics and Pathology, Rudbeck Laboratory , Uppsala, Sweden
                Author notes
                Correspondence: Lena Claesson-Welsh, Uppsala University, Department of Immunology, Genetics and Pathology, Rudbeck Laboratory , Dag Hammarskjöldsv. 20, 751 85 Uppsala, Sweden. E-mail: lena.welsh@ 123456igp.uu.se
                Article
                UPS_A_1064501_O
                10.3109/03009734.2015.1064501
                4526869
                26220421
                d024b8ef-5606-4df6-97a1-f9126b99d607
                © Informa Healthcare

                This is an open-access article distributed under the terms of the CC-BY-NC-ND 3.0 License which permits users to download and share the article for non-commercial purposes, so long as the article is reproduced in the whole without changes, and provided the original source is credited.

                History
                : 09 June 2015
                : 13 June 2015
                Categories
                Review Article

                Medicine
                edema,histamine,junctions,pore,vascular permeability,vegf
                Medicine
                edema, histamine, junctions, pore, vascular permeability, vegf

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