title: Different effects of angiotensin II and angiotensin-(1-7) on vascular smooth muscle cell proliferation and migration.
abstract: BACKGROUND
  Angiotensin (Ang) II and Ang-(1-7) are two of the bioactive peptides of the rennin-angiotensin system. Ang II is involved in the development of cardiovascular disease, such as hypertension and atherosclerosis, while Ang-(1-7) shows cardiovascular protection in contrast to Ang II.
  
  
  RESULTS
  In this study, we investigated effects of Ang II and Ang-(1-7) on vascular smooth muscle cell (SMC) proliferation and migration, which are critical in the formation of atherosclerotic lesions. Treatment with Ang II resulted in an increase of SMC proliferation, whereas Ang-(1-7) alone had no effects. However, preincubation with Ang-(1-7) inhibited Ang II-induced SMC proliferation. Ang II promoted SMC migration, and this effect was abolished by pretreatment with Ang-(1-7). The stimulatory effects of Ang II on SMC proliferation and migration were blocked by the Ang II receptor antagonist lorsartan, while the inhibitory effects of Ang-(1-7) were abolished by the Ang-(1-7) receptor antagonist A-799. Ang II treatment caused activation of ERK1/2 mediated signaling, and this was inhibited by preincubation of SMCs with Ang-(1-7).
  
  
  CONCLUSIONS
  These results suggest that Ang-(1-7) inhibits Ang II-induced SMC proliferation and migration, at least in part, through negative modulation of Ang II induced ERK1/2 activity.
authors.affiliation: William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Hu
authors.forename: Qingbo
authors.initials: Q
authors.lastname: Xu
authors.forename: Shu
authors.initials: S
authors.lastname: Ye
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism
chemical_list: C092006:7-Ala-angiotensin (1-7); D047228:Angiotensin II Type 1 Receptor Blockers; D010446:Peptide Fragments; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D000803:Angiotensin I; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C118790:angiotensin I (1-7)
references.citation: Hypertension. 2007 Dec;50(6):1093-8
references.pmid: 17984366
references.citation: Kidney Int. 2006 Jun;69(12):2212-8
references.pmid: 16672906
references.citation: Hypertension. 2001 Apr;37(4):1141-6
references.pmid: 11304516
references.citation: FASEB J. 2003 Nov;17(14):2106-8
references.pmid: 12958154
references.citation: Arterioscler Thromb Vasc Biol. 1997 Nov;17(11):2808-16
references.pmid: 9409259
references.citation: J Pharmacol Sci. 2007 Sep;105(1):74-81
references.pmid: 17895590
references.citation: J Clin Invest. 1995 Jul;96(1):141-9
references.pmid: 7615784
references.citation: Hypertension. 2001 Sep;38(3 Pt 2):660-4
references.pmid: 11566951
references.citation: Nat Rev Mol Cell Biol. 2005 Jan;6(1):56-68
references.pmid: 15688067
references.citation: Hypertension. 2000 Apr;35(4):998-1001
references.pmid: 10775575
references.citation: Am J Physiol. 1994 Aug;267(2 Pt 1):E260-7
references.pmid: 8074205
references.citation: Am J Physiol Heart Circ Physiol. 2007 Feb;292(2):H736-42
references.pmid: 17098828
references.citation: J Med Chem. 1989 Mar;32(3):520-2
references.pmid: 2918497
references.citation: Pharmacol Rev. 2000 Dec;52(4):639-72
references.pmid: 11121512
references.citation: Am J Physiol Heart Circ Physiol. 2006 Apr;290(4):H1651-9
references.pmid: 16284240
references.citation: Hypertension. 2001 Jan;37(1):72-76
references.pmid: 11208759
references.citation: J Hypertens. 2001 Nov;19(11):2001-9
references.pmid: 11677365
references.citation: Carcinogenesis. 2004 Nov;25(11):2045-52
references.pmid: 15284177
references.citation: J Hypertens. 1999 Jul;17(7):907-16
references.pmid: 10419063
references.citation: Am J Physiol Renal Physiol. 2010 Mar;298(3):F579-88
references.pmid: 20032116
references.citation: Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8258-63
references.pmid: 12829792
references.citation: Biochem Biophys Res Commun. 2009 Nov 6;389(1):138-44
references.pmid: 19715669
references.citation: Nat Protoc. 2007;2(2):329-33
references.pmid: 17406593
references.citation: Hypertension. 1996 Mar;27(3 Pt 2):523-8
references.pmid: 8613197
references.citation: Mol Cells. 2005 Oct 31;20(2):263-70
references.pmid: 16267402
references.citation: Cardiovasc Res. 2007 Feb 1;73(3):463-9
references.pmid: 17049503
references.citation: J Biol Chem. 2002 Mar 22;277(12):10452-8
references.pmid: 11784715
references.citation: Circ Res. 2001 Jun 8;88(11):1120-6
references.pmid: 11397777
references.citation: Circ Heart Fail. 2010 Mar;3(2):286-93
references.pmid: 20103774
references.citation: Arterioscler Thromb Vasc Biol. 1999 Jan;19(1):73-82
references.pmid: 9888869
references.citation: Hypertension. 1999 Oct;34(4 Pt 2):950-7
references.pmid: 10523390
references.citation: Nature. 2000 Sep 14;407(6801):233-41
references.pmid: 11001066
references.citation: Hypertension. 2003 Oct;42(4):574-9
references.pmid: 12953014
references.citation: Hypertension. 1999 Aug;34(2):296-301
references.pmid: 10454457
references.citation: Hypertension. 1996 Jul;28(1):104-8
references.pmid: 8675248
references.citation: Am J Physiol Heart Circ Physiol. 2005 Oct;289(4):H1560-6
references.pmid: 15951342
references.citation: Am Heart J. 2005 Jan;149(1):e2
references.pmid: 15660025
references.citation: Science. 1991 Sep 6;253(5024):1129-32
references.pmid: 1653454
references.citation: Circulation. 1999 Aug 24;100(8):861-8
references.pmid: 10458724
references.citation: Arterioscler Thromb Vasc Biol. 2000 Dec;20(12):2527-32
references.pmid: 11116048
references.citation: Arterioscler Thromb Vasc Biol. 2005 Sep;25(9):1831-6
references.pmid: 15994438
references.citation: J Biol Chem. 2003 Jun 20;278(25):22631-43
references.pmid: 12692126
references.citation: Exp Physiol. 2008 May;93(5):599-612
references.pmid: 18296491
references.citation: Hypertension. 2005 Jan;45(1):138-41
references.pmid: 15545510
references.citation: Mol Pharmacol. 2004 Apr;65(4):832-41
references.pmid: 15044612
references.citation: Haematologica. 2009 Jun;94(6):857-60
references.pmid: 19377080
references.citation: Hypertension. 1999 Jan;33(1 Pt 2):207-11
references.pmid: 9931106
references.citation: Am J Cardiol. 2001 Apr 19;87(8A):25C-32C
references.pmid: 11334765
references.citation: Circ Res. 2008 Nov 21;103(11):1319-26
references.pmid: 18845809
references.citation: J Pharmacol Exp Ther. 2010 Jan;332(1):116-24
references.pmid: 19797620
references.citation: Circ Res. 1991 Feb;68(2):450-6
references.pmid: 1991349
references.citation: Circ Res. 2002 Nov 1;91(9):852-9
references.pmid: 12411401