Pathophysiology of Haemostasis and Thrombosis
New Perspectives for Heparin
Endothelial Cell Matrices Modulate Smooth Muscle Cell Growth, Contractile Phenotype and Sensitivity to HeparinHerman I.M.Tufts University Health Science Schools, Program in Cell, Molecular and Developmental Biology, Boston, Mass., USA
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Article / Publication Details
Published online: April 24, 2009
Issue release date: 1990
Number of Print Pages: 12
Number of Figures: 0
Number of Tables: 0
ISSN: 1424-8832 (Print)
eISSN: 1424-8840 (Online)
For additional information: https://www.karger.com/PHT
Abstract
Whereas vascular smooth muscle cell-extracellular matrix interactions have been intensively studied, our knowledge regarding the role that matrix plays in regulating the growth state and contractile phenotype of vessel wall cells is fragmentary. Of particular interest has been the demonstrable ability of (1) heparin to selectively inhibit vascular smooth muscle cell growth in vitro; (2) aortic endothelial cells to produce a heparin-like inhibitor of vascular smooth muscle cells, and (3) heparin to reverse smooth muscle cell proliferation in arteries that have been experimentally denuded of their endothelium. Recent work from our laboratory indicates that the endothelial cell synthesized extracellular matrix alters growth rate and heparin sensitivity of vascular smooth muscle cells. Whereas endothelial cell synthesized matrices that contain collagen and fibronectin promote smooth muscle cell growth, matrices containing heparan sulfate proteoglycan selectively inhibit identical smooth muscle cell populations. Similarly, these heparan sulfate enriched matrices lower smooth muscle sensitivity to heparin and positively influence the endothelial cells’ ability to produce the heparin-like inhibitor of vascular smooth muscle cell growth. In an effort to understand the mechanism mediating heparin’s effects on smooth muscle cell proliferation and contractile phenotype, we have analyzed the effects of heparin on vascular smooth muscle cell shape and actin isoform expression using doses of heparin previously shown to be growth inhibitory. The results of our studies indicate that heparin alters smooth muscle cell shape and cytoskeletal organization, suggesting that heparin’s growth inhibitory action may be related to its effects on cell shape. Additionally, the permissive effects that different endothelial matrices exert on vascular smooth muscle may selectively predispose specific subpopulations of arterial cells towards a proliferating phenotype, one associated with the genesis of atherosclerosis.
© 1990 S. Karger AG, Basel
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Article / Publication Details
Published online: April 24, 2009
Issue release date: 1990
Number of Print Pages: 12
Number of Figures: 0
Number of Tables: 0
ISSN: 1424-8832 (Print)
eISSN: 1424-8840 (Online)
For additional information: https://www.karger.com/PHT
Copyright / Drug Dosage / Disclaimer
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.
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