Differential control of MMP and t-PA/PAI-1 expressions by sympathetic and renin-angiotensin systems in rat left ventricle.

Details

Serval ID
serval:BIB_6097A2126AD1
Type
Article: article from journal or magazin.
Collection
Publications
Title
Differential control of MMP and t-PA/PAI-1 expressions by sympathetic and renin-angiotensin systems in rat left ventricle.
Journal
Autonomic Neuroscience : Basic and Clinical
Author(s)
Dab H., Hachani R., Hodroj W., Sakly M., Bricca G., Kacem K.
ISSN
1872-7484[electronic], 1566-0702[linking]
Publication state
Published
Issued date
2009
Peer-reviewed
Oui
Volume
150
Number
1-2
Pages
27-32
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Abstract
In the present study, we tested the hypothesis that angiotensin II (Ang II) has both direct (via AT1 receptors) and indirect (via sympathostimulator pathway) actions on the synthesis and activity of the enzymes involved in the extracellular matrix degradation in vivo. For this purpose, sympathectomy and blockade of the Ang II receptor AT1 were performed alone or in combination in normotensive rats. The mRNA of the plasminogen activator (t-PA) and its inhibitor (PAI-1), the mRNA, protein and activity of the matrix metalloproteinases MMP-2 and MMP-9 were examined by Q-RT-PCR, immunoblotting and zymographic methods in the left ventricle. t-PA and PAI-1 mRNA were decreased after sympathectomy and remained unchanged after AT1 receptors blockade. mRNA was increased for t-PA and decreased by similar degree for PAI-1 after double treatment. MMPs mRNA and protein levels were decreased either after sympathectomy or AT1 receptors blockade and an additive effect was acquired after double treatment. MMPs activity was decreased by similar degree in the three treated groups. Deducted interpretations from our experimental approach suggest that Ang II inhibits directly (via AT1 receptors) and indirectly (via sympathostimulator pathway) t-PA mRNA synthesis. It seems unable to influence directly PAI-1 mRNA, but stimulates indirectly PAI-1 mRNA synthesis. Ang II stimulates directly (via AT1 receptors) and indirectly (via sympathostimulator pathway) MMPs synthesis at both transcriptional and protein levels. The enzymatic activity of MMPs does not seem to be influenced directly by Ang II but it could be stimulated indirectly (via sympathostimulator pathway).
Keywords
Analysis of Variance, Animals, Blood Pressure/drug effects, Blood Pressure/physiology, Body Weight/drug effects, Gene Expression Regulation/drug effects, Gene Expression Regulation/physiology, Guanethidine/pharmacology, Heart Ventricles/metabolism, Male, Matrix Metalloproteinase 2/genetics, Matrix Metalloproteinase 2/metabolism, Matrix Metalloproteinase 9/genetics, Matrix Metalloproteinase 9/metabolism, Matrix Metalloproteinases/genetics, Matrix Metalloproteinases/metabolism, Plasminogen Activator Inhibitor 1/genetics, Plasminogen Activator Inhibitor 1/metabolism, Plasminogen Activators/genetics, Plasminogen Activators/metabolism, RNA, Messenger/metabolism, Rats, Rats, Wistar, Renin-Angiotensin System/physiology, Sympathectomy/methods, Sympathetic Nervous System/drug effects, Sympathetic Nervous System/physiology, Sympatholytics/pharmacology
Pubmed
Create date
10/06/2010 14:08
Last modification date
20/08/2019 14:17
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