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      Regulation of the Fibrinolytic Potential of Cultured Human Umbilical Vein Endothelial Cells: Astragaloside IV Downregulates Plasminogen Activator Inhibitor-1 and Upregulates Tissue-Type Plasminogen Activator Expression

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          Abstract

          We have investigated whether the saponin astragaloside IV (AS-IV), a 3-0-β-D-xylopyranosyl-6-O- β -D-glucopyranosylcycloastragenol, purified from the Chinese herb drug Astragalus membranaceus, which is used in traditional Chinese medicine to treat cardiovascular diseases, might affect the fibrinolytic potential of cultured human umbilical vein endothelial cells (HUVECs). When HUVECs were conditioned with AS-IV, a dose (0.01–100 µg AS-IV/ ml)- and time-dependent decrease in plasminogen activator inhibitor type 1 (PAI-1) and an increase in tissue-type plasminogen activator (t-PA) synthesis were observed, which were significant from 1 µg AS-IV/ml and from 12 h of incubation with 100 µg AS-IV/ml. PAI-1 antigen decreased from 641 ± 86 to 318 ± 18 ng/l0<sup>5</sup> cells/24 h, whereas t-PA antigen increased from 4.1 ± 0.3 to 9.7 ± 0.4 ng/l0<sup>5</sup> cells/24 h after addition of 100 µg AS-IV/ml. PAI-1 activity decreased to 30% of control level, whereas t-PA activity and t-PA-PAI-1 complexes reached a maximum stimulation of 3- and 5-fold over control levels, respectively, in the conditioned media of HUVECs treated with 100 µg AS-IV/ml for 24 h. PAI-1-specific mRNA expression decreased to 55% (2.2 kb) and 72% (3.2 kb), 66% (2.2 kb) and 88% (3.2 kb), and 19% (2.2 kb) and 41% (3.2 kb) of control values after incubation for 6, 12 and 18 h, respectively, whereas t-PA-specific mRNA increased 2-, 2.5- and 1.4-fold in HUVECs treated with 100 µg/ml AS-IV for 6, 12, and 18 h, respectively. In conclusion our data give evidence that in fact AS-IV can increase the fibrinolytic potential of cultured HUVECs not only by upregulating the expression of t-PA as NG-Rl does, but also by downregulating the expression of PAI-1.

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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
          1997
          1997
          24 September 2008
          : 34
          : 4
          : 273-280
          Affiliations
          aDepartment of Vascular Biology and Thrombosis Research, University of Vienna, Austria; and bDepartment of Physiology, Beijing University of Traditional Chinese Medicine, Beijing, P.R. China
          Article
          159234 J Vasc Res 1997;34:273–280
          10.1159/000159234
          9256087
          © 1997 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
          Pages: 8
          Categories
          Research Paper

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