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      Correlation of Pulmonary Arterial Smooth Muscle Structure and Reactivity during Adaptation to Extrauterine Life

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          Abstract

          Peripheral pulmonary arteries remodel immediately after birth as pulmonary vascular resistance falls. We hypothesised that there is a link between the response to agonist stimulation and wall structure in early postnatal life. Arteries from fetal, newborn and 14-day-old piglets were mounted on a perfusion myograph. Lumen diameter and smooth muscle cell nuclear positions were recorded after sequential addition of KCl, U46619 and bradykinin. Subsequently, vessels were studied by confocal and transmission electron microscopy. Contractile agonist stimulation caused a greater and faster reduction in lumen diameter in the newborn than at 14 days (p < 0.02) and the distance between cells decreased more in the newborn (p < 0.05). Unstimulated smooth muscle cells changed shape from being rounded in the fetus to fusiform by 14 days, with increasing length/width ratio (p < 0.01). On contraction, length/width ratio decreased most at 14 days (p < 0.01). Extracellular matrix, collagen and elastin, sparse at birth, increased by 14 days. Thus a greater change in lumen diameter in relation to cellular contraction was observed in the newborn than at 14 days and the amount of extracellular matrix within the vessel wall may affect the overall change in lumen diameter.

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          Integrin-ligand binding properties govern cell migration speed through cell-substratum adhesiveness.

          Migration of cells in higher organisms is mediated by adhesion receptors, such as integrins, that link the cell to extracellular-matrix ligands, transmitting forces and signals necessary for locomotion. Whether cells will migrate or not on a given substratum, and also their speed, depends on several variables related to integrin-ligand interactions, including ligand levels, integrin levels, and integrin-ligand binding affinities. These and other factors affect the way molecular systems integrate to effect and regulate cell migration. Here we show that changes in cell migration speed resulting from three separate variables-substratum ligand level, cell integrin expression level, and integrin-ligand binding affinity-are all quantitatively predictable through the changes they cause in a single unifying parameter: short-term cell-substratum adhesion strength. This finding is consistent with predictions of a mathematical model for cell migration. The ligand concentration promoting maximum migration speed decreases reciprocally as integrin expression increases. Increases in integrin-ligand affinity similarly result in maximal migration at reciprocally lower ligand concentrations. The maximum speed attainable, however, remains unchanged as ligand concentration, integrin expression, or integrin-ligand affinity vary, suggesting that integrin coupling with intracellular motors remains unaltered.
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            Author and article information

            Journal
            JVR
            J Vasc Res
            10.1159/issn.1018-1172
            Journal of Vascular Research
            S. Karger AG
            1018-1172
            1423-0135
            2002
            February 2002
            13 February 2002
            : 39
            : 1
            : 30-40
            Affiliations
            Unit of Vascular Biology and Pharmacology, Institute of Child Health, London, UK
            Article
            48991 J Vasc Res 2002;39:30–40
            10.1159/000048991
            11844935
            © 2002 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.

            Page count
            Figures: 7, References: 30, Pages: 11
            Categories
            Research Paper

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