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      VEGF-A in Cardiomyocytes and Heart Diseases

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          Abstract

          The vascular endothelial growth factor (VEGF), a homodimeric vasoactive glycoprotein, is the key mediator of angiogenesis. Angiogenesis, the formation of new blood vessels, is responsible for a wide variety of physio/pathological processes, including cardiovascular diseases (CVD). Cardiomyocytes (CM), the main cell type present in the heart, are the source and target of VEGF-A and express its receptors, VEGFR1 and VEGFR2, on their cell surface. The relationship between VEGF-A and the heart is double-sided. On the one hand, VEGF-A activates CM, inducing morphogenesis, contractility and wound healing. On the other hand, VEGF-A is produced by CM during inflammation, mechanical stress and cytokine stimulation. Moreover, high concentrations of VEGF-A have been found in patients affected by different CVD, and are often correlated with an unfavorable prognosis and disease severity. In this review, we summarized the current knowledge about the expression and effects of VEGF-A on CM and the role of VEGF-A in CVD, which are the most important cause of disability and premature death worldwide. Based on clinical studies on angiogenesis therapy conducted to date, it is possible to think that the control of angiogenesis and VEGF-A can lead to better quality and span of life of patients with heart disease.

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          Most cited references167

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          The biology of vascular endothelial growth factor.

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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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              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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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                26 July 2020
                August 2020
                : 21
                : 15
                : 5294
                Affiliations
                [1 ]Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, 80131 Naples, Italy; brailemariantonia@ 123456gmail.com (M.B.); s.marcella92@ 123456gmail.com (S.M.); l.cristinziano@ 123456gmail.com (L.C.); mrgaldiero@ 123456libero.it (M.R.G.); modestino.luca@ 123456gmail.com (L.M.); anneliseferrara@ 123456gmail.com (A.L.F.); gildanet@ 123456gmail.com (G.V.)
                [2 ]WAO Center of Excellence, 80131 Naples, Italy
                [3 ]CNR Institute of Experimental Endocrinology and Oncology “G. Salvatore”, 80131 Naples, Italy
                [4 ]Department of Public Health, University of Naples Federico II, 80131 Naples, Italy; gcmarone@ 123456hotmail.it
                [5 ]Azienda Ospedaliera Ospedali dei Colli – Monaldi Hospital Pharmacy, 80131 Naples, Italy
                Author notes
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-9285-4657
                https://orcid.org/0000-0002-5871-1898
                Article
                ijms-21-05294
                10.3390/ijms21155294
                7432634
                32722551
                4f3a2331-6e9f-46cc-920a-8ec52f360227
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 08 June 2020
                : 22 July 2020
                Categories
                Review

                Molecular biology
                angiogenesis,atherosclerosis,cardiovascular disease,inflammation,ischemic heart disease,myocardial infarction

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