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

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

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
Published online on: November 14, 2014 https://doi.org/10.3892/mmr.2014.2952
Pages: 1587-1594
Copyright: © Guo et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

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.

View Figures

View References

1	Peeters W, Moll FL, Vink A, et al: Collagenase matrix metalloproteinase-8 expressed in atherosclerotic carotid plaques is associated with systemic cardiovascular outcome. Eur Heart J. 32:2314–2325. 2011. View Article : Google Scholar : PubMed/NCBI
2	Siasos G, Tousoulis D, Kioufis S, et al: Inflammatory mechanisms in atherosclerosis: the impact of matrix metalloproteinases. Curr Top Med Chem. 12:1132–1148. 2012. View Article : Google Scholar : PubMed/NCBI
3	Newby AC: Dual role of matrix metalloproteinases (matrixins) in intimal thickening and atherosclerotic plaque rupture. Physiol Rev. 85:1–31. 2005. View Article : Google Scholar
4	Yu YM and Lin HC: Curcumin prevents human aortic smooth muscle cells migration by inhibiting of MMP-9 expression. Nutr Metab Cardiovasc Dis. 20:125–132. 2010. View Article : Google Scholar
5	Johnson JL, Dwivedi A and Somerville M: Matrix metalloproteinase (MMP)-3 activates MMP-9 mediated vascular smooth muscle cell migration and neointima formation in mice. Arterioscler Thromb Vasc Biol. 31:e35–e44. 2011. View Article : Google Scholar : PubMed/NCBI
6	An J, Nakajima T, Kuba K and Kimura A: Losartan inhibits LPS-induced inflammatory signaling through a PPARγ-dependent mechanism in human THP-1 macrophages. Hypertens Res. 33:831–835. 2010. View Article : Google Scholar : PubMed/NCBI
7	Díez J: Review of the molecular pharmacology of Losartan and its possible relevance to stroke prevention in patients with hypertension. Clin Ther. 28:832–848. 2006. View Article : Google Scholar : PubMed/NCBI
8	Hernandez-Trujillo Y1, Rodriguez-Esparragon F, Macias-Reyes A, Caballero-Hidalgo A and Rodriguez-Perez JC: Rosiglitazone but not losartan prevents Nrf-2 dependent CD36 gene expression up-regulation in an in vivo atherosclerosis model. Cardiovasc Diabetol. 7:32008. View Article : Google Scholar : PubMed/NCBI
9	Xu YM, Deepak S, Li GP and Zhao YN: Effect of angiotensin II type 1 receptor antagonist, losartan on inflammatory factor in atherosclerotic rabbits. Res Cardiocvasc Med. 1:127–131. 2013. View Article : Google Scholar
10	Xu HX, Li JJ, Li GS, et al: Decreased infiltration of macrophages and inhibited activation of nuclear factor-kappa B in blood vessels: a possible mechanism for the anti-atherogenic effects of losartan. Acta Cardiol. 62:607–613. 2007. View Article : Google Scholar
11	Luan Z, Chase AJ and Newby AC: Statins inhibit secretion of metalloproteinases-1, -2, -3, and -9 from vascular smooth muscle cells and macrophages. Arterioscler Thromb Vasc Biol. 23:769–775. 2003. View Article : Google Scholar : PubMed/NCBI
12	Madala SK, Pesce JT, Ramalingam TR, et al: Matrix metalloproteinase 12-deficiency augments extracellular matrix degrading metalloproteinases and attenuates IL-13-dependent fibrosis. J Immunol. 184:3955–3963. 2010. View Article : Google Scholar : PubMed/NCBI
13	Yang DC, Ma ST and Tan Y: Imbalance of matrix metalloproteinases/tissue inhibitor of metalloproteinase-1 and loss of fibronectin expression in patients with congestive heart failure. Cardiology. 116:133–141. 2010. View Article : Google Scholar : PubMed/NCBI
14	Dabek J, Glogowska-Ligus J and Szadorska B: Transcription activity of MMP-2 and MMP-9 metalloproteinase genes and their tissue inhibitor (TIMP-2) in acute coronary syndrome patients. J Postgrad Med. 59:115–120. 2013. View Article : Google Scholar : PubMed/NCBI
15	Ding SF, Liu HJ, Lu Q, et al: Changes of matrix metalloproteinase-9 and tissue inhibitors of metalloproteinase-1 during left ventricular remodeling in acute myocardial infarction patients after percutaneous coronary intervention. Biomed Res-India. 24:179–184. 2013.
16	Virdis A, Duranti E and Taddei S: Oxidative stress and vascular damage n hypertension: Role of angiotensin II. Int J Hypertens. 2011.Epub, 2011. View Article : Google Scholar
17	Lee BS, Choi JY, Kim JY, et al: Simvastatin and losartan differentially and synergistically inhibit atherosclerosis in apolipoprotein e(−/−) mice. Korean Circ J. 42:543–550. 2012. View Article : Google Scholar : PubMed/NCBI
18	Kaynar K, Ulusoy S, Ovali E, et al: TGF-beta and TNF-alpha producing effects of losartan and amlodipine on human mononuclear cell culture. Nephrology (Carlton). 10:478–482. 2005. View Article : Google Scholar
19	Yaghooti H, Firoozrai M, Fallah S and Khorramizadeh MR: Angiotensin II differentially induces matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 production and disturbs MMP/TIMP balance. Avicenna J Med Biotechnol. 2:79–85. 2010.PubMed/NCBI
20	Gu J, Liu X, Wang QX, et al: Angiotensin II increases CTGF expression via MAPKs/TGF-β1/TRAF6 pathway in atrial fibroblasts. Exp Cell Res. 318:2105–2015. 2012. View Article : Google Scholar : PubMed/NCBI
21	O’Reilly MA: Angiotensin II: tapping the cell cycle machinery to kill endothelial cells. Am J Physiol Lung Cell Mol Physiol. 303:L575–L576. 2012. View Article : Google Scholar :
22	deBlois D, Tea BS, Than VD, Tremblay J and Hamet P: Smooth muscle apoptosis during vascular regression in spontaneously hypertensive rats. Hypertension. 29:340–349. 1997. View Article : Google Scholar : PubMed/NCBI
23	Hadler-Olsen E, Fadnes B, Sylte I, Uhlin-Hansen L and Winberg JO: Regulation of matrix metalloproteinase activity in health and disease. FEBS J. 278:28–45. 2011. View Article : Google Scholar
24	Morand-Contant M, Anand-Srivastava MB and Couture R: Kinin B1 receptor upregulation by angiotensin II and endothelin-1 in rat vascular smooth muscle cells: receptors and mechanisms. Am J Physiol Heart Circ Physiol. 299:H1625–H1632. 2010. View Article : Google Scholar : PubMed/NCBI
25	Pan P, Fu H, Zhang L, et al: Angiotensin II upregulates the expression of placental growth factor in human vascular endothelial cells and smooth muscle cells. BMC Cell Biol. 11:362010. View Article : Google Scholar : PubMed/NCBI
26	Kranzhoeter R and Larsen D: Angiotensin II induces relaease of matrix metalloproteinases from human vascular smooth muscle cells via NF-kappa B. Circulation. 102:11–12. 2000.