Impact of losartan and angiotensin II on the expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in rat vascular smooth muscle cells

Guo,Yan-Song; Wu,Zong-Gui; Yang,Jun-Ke; Chen,Xin-Jing

doi:10.3892/mmr.2014.2952

March-2015 Volume 11 Issue 3

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March-2015 Volume 11 Issue 3

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Article Open Access

Impact of losartan and angiotensin II on the expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in rat vascular smooth muscle cells

Authors:
- Yan-Song Guo
- Zong-Gui Wu
- Jun-Ke Yang
- Xin-Jing Chen
View Affiliations / Copyright

Affiliations: Department of Cardiology, Provincial Clinical Medical College of Fujian Medical University, Fujian Institute of Cardiovascular Disease, Fujian Provincial Hospital, Fuzhou 350001, P.R. China, Department of Cardiology, Changzheng Hospital, Second Military Medical University, Shanghai 200433, P.R. China, Department of Cardiology, General Hospital of PLA Second Artillery, Beijing 100088, P.R. China

Copyright: © Guo et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
Pages: 1587-1594
|
Published online on: November 14, 2014

https://doi.org/10.3892/mmr.2014.2952
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Abstract

The present study aimed to investigate the impact of losartan and angiotensin II (AngII) on the expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1), secreted by rat vascular smooth muscle cells (VSMCs). Rat VSMCs were isolated and cultured in different concentrations of AngII and losartan for 24 h and western blot analysis and quantitative polymerase chain reaction were performed to observe the subsequent impact on the gene and protein expression of MMP-9 and TIMP-1. AngII was shown to promote the protein and gene expression of MMP-9 in VSMCs in a concentration-dependent manner. No effect was observed on the expression of TIMP-1, therefore, an increase in the MMP-9/TIMP-1 ratio was observed. Losartan was shown to be able to inhibit MMP-9 protein and gene expression in a concentration-dependent manner, whilst promoting an increase in TIMP-1 expression, thus decreasing the ratio of MMP-9/TIMP-1. The combined action of losartan and AngII resulted in the same directional changes in MMP-9 and TIMP-1 expression as observed for losartan alone. The comparison of AngII, losartan and the combinatory effect on the expression of MMP-9 and TIMP-1 in VSMCs indicated that losartan inhibited the effects of AngII, therefore reducing the MMP-9/TIMP-1 ratio, which may contribute to the molecular mechanism of losartan in preventing atherosclerosis. In atherosclerosis, the development of the extracellular matrix of plaque is closely correlated with the evolution of AS. The balance between MMPs and TIMPs is important in maintaining the dynamic equilibrium between the ECM, and the renin-angiotensin-aldosterone system, which is involved in the pathologenesis of AS, and in which AngII has a central role.

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