Cellular Physiology and Biochemistry
Original Paper
Tissue Inhibitor of Matrix Metalloproteinase-1 in Norepinephrine-Induced Remodeling of the Mouse HeartMeier H.1 · Bullinger J.1 · Deten A.1 · Marx G.1 · Rabald S.1 · Zimmer H.-G.1 · Briest W.1,21Carl-Ludwig-Institute of Physiology, University of Leipzig,2current address: Laboratory of Cardiovascular Sciences, National Institute on Aging, Baltimore,*These authors contributed equally to this study
Wilfried Briest, Ph.D. LCS / GRC / NIA / NIH, 5600 Nathan Shock Drive Baltimore, MD 21224 (USA) Tel. + 1-410-558-8305, Fax: + 1-410-558-8150 E-Mail briestw@mail.nih.gov |
|
Abstract
Background: Matrix metalloproteinases (MMPs) play an important role in myocardial remodeling. Their activity is regulated by the tissue inhibitors of metalloproteinases (TIMPs). The present study analyzed the contribution of changes in functional and molecular parameters to early cardiac remodeling in mice hearts. The role that TIMPs might play in this process was specially acknowledged. Methods: The remodeling was induced by norepinephrine (NE) given sc in balb/c mice. Varying concentrations, time and the addition of a neutralizing TIMP-1 antibody were evaluated. Results: High dose NE led to insufficiency of the left ventricle (LV) as evidenced by reduced NE-induced elevation of LV systolic pressure, contractility and relaxation. Further, signs of lung congestion were seen. NE induced a concentration-dependent increase of LV weight/body weight (LVW/BW) ratio and elevated mRNA expression of atrial natriuretic peptide (ANP). This was accompanied by induction of collagen type I and III, as well as TIMP-1 expression. Conclusions: The NE-induced increase of TIMP-1 expression may induce the elevation of the antihypertrophic cardiac factor ANP since NE-induced increase of ANP expression was abolished by neutralizing TIMP-1 antibody. Thus, TIMP-1 may mediate ANP-induced attenuation of NE-induced hypertrophy in the mouse heart.
© 2007 S. Karger AG, Basel
Related Articles:
Article / Publication Details
Published online: October 30, 2007
Issue release date: October 2007
Number of Print Pages: 12
Number of Figures: 0
Number of Tables: 0
ISSN: 1015-8987 (Print)
eISSN: 1421-9778 (Online)
For additional information: https://www.karger.com/CPB
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.
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.

Get Permission