Physiological regulation of MMPs and tPA/PAI in the arterial wall of rats by noradrenergic tone and angiotensin II
The interactions between the sympathetic nervous system (SNS) and angiotensin II (ANG II), and their direct effects in vitro on the enzymes involved in vascular extracellular matrix (ECM) degradation, were examined. Rats were treated with guanethidine, losartan or the combined treatments. mRNA, prot...
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Format: | Article |
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SAGE Publications
2012-03-01
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Series: | Journal of the Renin-Angiotensin-Aldosterone System |
Online Access: | https://doi.org/10.1177/1470320311428344 |
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author | Houcine Dab Rafik Hachani Nedra Dhaouadi Wassim Hodroj Mohsen Sakly Jacques Randon Giampiero Bricca Kamel Kacem |
author_facet | Houcine Dab Rafik Hachani Nedra Dhaouadi Wassim Hodroj Mohsen Sakly Jacques Randon Giampiero Bricca Kamel Kacem |
author_sort | Houcine Dab |
collection | DOAJ |
description | The interactions between the sympathetic nervous system (SNS) and angiotensin II (ANG II), and their direct effects in vitro on the enzymes involved in vascular extracellular matrix (ECM) degradation, were examined. Rats were treated with guanethidine, losartan or the combined treatments. mRNA, protein and activity of matrix metalloproteinase (MMP)-2 and MMP-9 and mRNA of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) were quantified in abdominal aorta (AA) and femoral artery (FA). Norepinephrine (NE) or ANG II with adrenergic (β, α1 and α2) or losartan antagonists was tested for MMP mRNA response in cultured vascular smooth muscle cells (VSMCs). Combined treatment enhances the inhibition of MMP-2 mRNA and protein level induced by simple treatment in AA. However MMP-9 in AA and MMP mRNA in FA were reduced in the same order by treatments. MMP activities were not affected by treatments. The t-PA/PAI-1 ratio, which reflects the fibrinolytic balance, remained higher after treatments. In cultured VSMCs, NE induced stimulation of MMP mRNA via α2 and β adrenergic receptors and MMP-2 activity via β adrenergic receptors, while ANG II-induced stimulation was abrogated by losartan. Overall, there is a synergic inhibition of both systems on the level of MMP-2 in AA. |
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language | English |
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spelling | doaj.art-ff52591d55f1425ead63e38396867a032024-03-02T12:42:30ZengSAGE PublicationsJournal of the Renin-Angiotensin-Aldosterone System1470-32031752-89762012-03-011310.1177/1470320311428344Physiological regulation of MMPs and tPA/PAI in the arterial wall of rats by noradrenergic tone and angiotensin IIHoucine Dab0Rafik Hachani1Nedra Dhaouadi2Wassim Hodroj3Mohsen Sakly4Jacques Randon5Giampiero Bricca6Kamel Kacem7INSERM ERI-22, Agressions Vasculaires et Réponses Tissulaires, Université de Claude Bernard, Lyon I, FranceUniversité de Carthage, Unité de Physiologie Intégrée, Laboratoire de Pathologies Vasculaires, Faculté des Sciences de Bizerte, TunisiaINSERM ERI-22, Agressions Vasculaires et Réponses Tissulaires, Université de Claude Bernard, Lyon I, FranceINSERM ERI-22, Agressions Vasculaires et Réponses Tissulaires, Université de Claude Bernard, Lyon I, FranceUniversité de Carthage, Unité de Physiologie Intégrée, Laboratoire de Pathologies Vasculaires, Faculté des Sciences de Bizerte, TunisiaINSERM ERI-22, Agressions Vasculaires et Réponses Tissulaires, Université de Claude Bernard, Lyon I, FranceINSERM ERI-22, Agressions Vasculaires et Réponses Tissulaires, Université de Claude Bernard, Lyon I, FranceUniversité de Carthage, Unité de Physiologie Intégrée, Laboratoire de Pathologies Vasculaires, Faculté des Sciences de Bizerte, TunisiaThe interactions between the sympathetic nervous system (SNS) and angiotensin II (ANG II), and their direct effects in vitro on the enzymes involved in vascular extracellular matrix (ECM) degradation, were examined. Rats were treated with guanethidine, losartan or the combined treatments. mRNA, protein and activity of matrix metalloproteinase (MMP)-2 and MMP-9 and mRNA of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) were quantified in abdominal aorta (AA) and femoral artery (FA). Norepinephrine (NE) or ANG II with adrenergic (β, α1 and α2) or losartan antagonists was tested for MMP mRNA response in cultured vascular smooth muscle cells (VSMCs). Combined treatment enhances the inhibition of MMP-2 mRNA and protein level induced by simple treatment in AA. However MMP-9 in AA and MMP mRNA in FA were reduced in the same order by treatments. MMP activities were not affected by treatments. The t-PA/PAI-1 ratio, which reflects the fibrinolytic balance, remained higher after treatments. In cultured VSMCs, NE induced stimulation of MMP mRNA via α2 and β adrenergic receptors and MMP-2 activity via β adrenergic receptors, while ANG II-induced stimulation was abrogated by losartan. Overall, there is a synergic inhibition of both systems on the level of MMP-2 in AA.https://doi.org/10.1177/1470320311428344 |
spellingShingle | Houcine Dab Rafik Hachani Nedra Dhaouadi Wassim Hodroj Mohsen Sakly Jacques Randon Giampiero Bricca Kamel Kacem Physiological regulation of MMPs and tPA/PAI in the arterial wall of rats by noradrenergic tone and angiotensin II Journal of the Renin-Angiotensin-Aldosterone System |
title | Physiological regulation of MMPs and tPA/PAI in the arterial wall of rats by noradrenergic tone and angiotensin II |
title_full | Physiological regulation of MMPs and tPA/PAI in the arterial wall of rats by noradrenergic tone and angiotensin II |
title_fullStr | Physiological regulation of MMPs and tPA/PAI in the arterial wall of rats by noradrenergic tone and angiotensin II |
title_full_unstemmed | Physiological regulation of MMPs and tPA/PAI in the arterial wall of rats by noradrenergic tone and angiotensin II |
title_short | Physiological regulation of MMPs and tPA/PAI in the arterial wall of rats by noradrenergic tone and angiotensin II |
title_sort | physiological regulation of mmps and tpa pai in the arterial wall of rats by noradrenergic tone and angiotensin ii |
url | https://doi.org/10.1177/1470320311428344 |
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