Different effects of angiotensin II and angiotensin-(1-7) on vascular smooth muscle cell proliferation and migration.
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.
Zhang
Feng
F
William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
Hu
Yanhua
Y
Xu
Qingbo
Q
Ye
Shu
S
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
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)
Hypertension. 2007 Dec;50(6):1093-8
17984366
Kidney Int. 2006 Jun;69(12):2212-8
16672906
Hypertension. 2001 Apr;37(4):1141-6
11304516
FASEB J. 2003 Nov;17(14):2106-8
12958154
Arterioscler Thromb Vasc Biol. 1997 Nov;17(11):2808-16
9409259
J Pharmacol Sci. 2007 Sep;105(1):74-81
17895590
J Clin Invest. 1995 Jul;96(1):141-9
7615784
Hypertension. 2001 Sep;38(3 Pt 2):660-4
11566951
Nat Rev Mol Cell Biol. 2005 Jan;6(1):56-68
15688067
Hypertension. 2000 Apr;35(4):998-1001
10775575
Am J Physiol. 1994 Aug;267(2 Pt 1):E260-7
8074205
Am J Physiol Heart Circ Physiol. 2007 Feb;292(2):H736-42
17098828
J Med Chem. 1989 Mar;32(3):520-2
2918497
Pharmacol Rev. 2000 Dec;52(4):639-72
11121512
Am J Physiol Heart Circ Physiol. 2006 Apr;290(4):H1651-9
16284240
Hypertension. 2001 Jan;37(1):72-76
11208759
J Hypertens. 2001 Nov;19(11):2001-9
11677365
Carcinogenesis. 2004 Nov;25(11):2045-52
15284177
J Hypertens. 1999 Jul;17(7):907-16
10419063
Am J Physiol Renal Physiol. 2010 Mar;298(3):F579-88
20032116
Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8258-63
12829792
Biochem Biophys Res Commun. 2009 Nov 6;389(1):138-44
19715669
Nat Protoc. 2007;2(2):329-33
17406593
Hypertension. 1996 Mar;27(3 Pt 2):523-8
8613197
Mol Cells. 2005 Oct 31;20(2):263-70
16267402
Cardiovasc Res. 2007 Feb 1;73(3):463-9
17049503
J Biol Chem. 2002 Mar 22;277(12):10452-8
11784715
Circ Res. 2001 Jun 8;88(11):1120-6
11397777
Circ Heart Fail. 2010 Mar;3(2):286-93
20103774
Arterioscler Thromb Vasc Biol. 1999 Jan;19(1):73-82
9888869
Hypertension. 1999 Oct;34(4 Pt 2):950-7
10523390
Nature. 2000 Sep 14;407(6801):233-41
11001066
Hypertension. 2003 Oct;42(4):574-9
12953014
Hypertension. 1999 Aug;34(2):296-301
10454457
Hypertension. 1996 Jul;28(1):104-8
8675248
Am J Physiol Heart Circ Physiol. 2005 Oct;289(4):H1560-6
15951342
Am Heart J. 2005 Jan;149(1):e2
15660025
Science. 1991 Sep 6;253(5024):1129-32
1653454
Circulation. 1999 Aug 24;100(8):861-8
10458724
Arterioscler Thromb Vasc Biol. 2000 Dec;20(12):2527-32
11116048
Arterioscler Thromb Vasc Biol. 2005 Sep;25(9):1831-6
15994438
J Biol Chem. 2003 Jun 20;278(25):22631-43
12692126
Exp Physiol. 2008 May;93(5):599-612
18296491
Hypertension. 2005 Jan;45(1):138-41
15545510
Mol Pharmacol. 2004 Apr;65(4):832-41
15044612
Haematologica. 2009 Jun;94(6):857-60
19377080
Hypertension. 1999 Jan;33(1 Pt 2):207-11
9931106
Am J Cardiol. 2001 Apr 19;87(8A):25C-32C
11334765
Circ Res. 2008 Nov 21;103(11):1319-26
18845809
J Pharmacol Exp Ther. 2010 Jan;332(1):116-24
19797620
Circ Res. 1991 Feb;68(2):450-6
1991349
Circ Res. 2002 Nov 1;91(9):852-9
12411401