Cellular Physiology and Biochemistry

Original Paper

Free Access

Tissue Inhibitor of Matrix Metalloproteinase-1 in Norepinephrine-Induced Remodeling of the Mouse Heart

Meier H.1 · Bullinger J.1 · Deten A.1 · Marx G.1 · Rabald S.1 · Zimmer H.-G.1 · Briest W.1,2

Author affiliations

1Carl-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

Corresponding Author

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

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Cell Physiol Biochem 2007;20:825–836

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




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Article / Publication Details

First-Page Preview
Abstract of Original Paper

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


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