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      Pathophysiologic Role of Molecules Determining Arteriovenous Differentiation in Adult Life


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          The structural differences between arteries and veins are genetically predetermined. Vascular identity markers, the molecular markers specific to veins and arteries, determine the differential development of vessels during embryogenesis and their expression persists in adult vessels. It is revealed that they can be reactivated under various pathophysiologic conditions even after vessel differentiation. Thus, once considered as quiescent in adults, vascular identity markers may actually play significant roles in vascular remodeling. Manipulation of vascular identity and the underlying molecular mechanisms might be a novel strategy to improve vascular remodeling for clinical application.

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          Most cited references67

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          Molecular distinction and angiogenic interaction between embryonic arteries and veins revealed by ephrin-B2 and its receptor Eph-B4.

          The vertebrate circulatory system is composed of arteries and veins. The functional and pathological differences between these vessels have been assumed to reflect physiological differences such as oxygenation and blood pressure. Here we show that ephrin-B2, an Eph family transmembrane ligand, marks arterial but not venous endothelial cells from the onset of angiogenesis. Conversely, Eph-B4, a receptor for ephrin-B2, marks veins but not arteries. ephrin-B2 knockout mice display defects in angiogenesis by both arteries and veins in the capillary networks of the head and yolk sac as well as in myocardial trabeculation. These results provide evidence that differences between arteries and veins are in part genetically determined and suggest that reciprocal signaling between these two types of vessels is crucial for morphogenesis of the capillary beds.
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            Endothelial cells and VEGF in vascular development.

            The intricate patterning processes that establish the complex vascular system during development depend on a combination of intrinsic pre-patterning and extrinsic responses to environmental parameters. Mutational studies in mice and fish have shown that the vascular system is highly sensitive to genetic disruption and have identified potential targets for therapeutic interventions. New insights into non-vascular roles of vascular endothelial growth factor and the requirement for endothelial cells in adult organs and stem-cell niches highlight possible side effects of anti-angiogenic therapy and the need for new targets.
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              Sensory nerves determine the pattern of arterial differentiation and blood vessel branching in the skin.

              Nerves and blood vessels are branched structures, but whether their branching patterns are established independently or coordinately is not clear. Here we show that arteries, but not veins, are specifically aligned with peripheral nerves in embryonic mouse limb skin. Mutations that eliminate peripheral sensory nerves or Schwann cells prevent proper arteriogenesis, while those that disorganize the nerves maintain the alignment of arteries with misrouted axons. In vitro, sensory neurons or Schwann cells can induce arterial marker expression in isolated embryonic endothelial cells, and VEGF(164/120) is necessary and sufficient to mediate this induction. These data suggest that peripheral nerves provide a template that determines the organotypic pattern of blood vessel branching and arterial differentiation in the skin, via local secretion of VEGF.

                Author and article information

                J Vasc Res
                Journal of Vascular Research
                S. Karger AG
                September 2020
                12 June 2020
                : 57
                : 5
                : 245-253
                [_a] aNuclear Medicine Department, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
                [_b] bDonnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada
                [_c] cVascular Surgery Department, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
                [_d] dDepartment of Cardiology, The Affiliated Hospital of Hangzhou Normal University, Institute of Ageing Research, School of Medicine, Hangzhou Normal University, Hangzhou, China
                [_e] eDepartment of Cell Physiology, The Jikei University School of Medicine, Tokyo, Japan
                Author notes
                *Dr. Ping Lü, Tongji Medical College, Huazhong University of Science and Technology, Vascular Surgery Department, Union Hospital, Jiefang Dadao Ave 1277, Wuhan 430022 (China), lvping2013@aliyun.com
                507627 J Vasc Res 2020;57:245–253
                © 2020 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                : 22 July 2019
                : 26 March 2020
                Page count
                Figures: 2, Tables: 1, Pages: 9
                Review Article

                General medicine,Neurology,Cardiovascular Medicine,Internal medicine,Nephrology
                Identity,Vascular remodeling,Vascular development,Eph-B4,Ephrin-B2


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