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Citations to this article

The angiotensin AT2-receptor mediates inhibition of cell proliferation in coronary endothelial cells.
M Stoll, … , R Metzger, T Unger
M Stoll, … , R Metzger, T Unger
Published February 1, 1995
Citation Information: J Clin Invest. 1995;95(2):651-657. https://doi.org/10.1172/JCI117710.
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The angiotensin AT2-receptor mediates inhibition of cell proliferation in coronary endothelial cells.

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Abstract

Angiotensin II (ANG II) is known to be a potent growth promoting factor for vascular smooth muscle cells and fibroblasts but little is known about its influence on growth in endothelial cells. We studied the effects of ANG II on endothelial growth and the role of the angiotensin receptor subtypes involved. Proliferation of rat coronary endothelial cells (CEC) and rat vascular smooth muscle cells (VSMC) was determined by [3H]thymidine incorporation, the MTT-test and by directly counting cells in a coulter counter. Angiotensin AT1- and AT2-receptors were demonstrated by binding studies and by the presence of their respective mRNA through reverse transcription polymerase chain reaction (RT-PCR). In contrast to VSMC, which in culture only express the AT1-receptor, CEC express both, AT1- and AT2-receptors simultaneously up to the third passage. Whereas ANG II stimulated growth of quiescent VSMC, an effect abolished by pretreatment with the AT1-receptor antagonist, losartan, ANG II did not induce proliferation in quiescent CEC. However, after pretreatment of quiescent endothelial cells (< passage 4) with the AT2-receptor antagonist, PD 123177, ANG II induced proliferation. This effect was reversed by additional pretreatment with losartan. ANG II significantly inhibited the proliferation of bFGF-stimulated CEC in a dose-dependent manner by maximally 50%. This effect was prevented by PD 123177 while losartan was ineffective. The AT2-receptor agonist, CGP 42112, mimicked the antiproliferative actions of ANG II, confirming the specificity of the effect. Our results show that the growth modulating actions of ANG II depend on the type of angiotensin receptor present on a given cell. In coronary endothelial cells, the antiproliferative actions of the AT2-receptor offset the growth promoting effects mediated by the AT1-receptor.

Authors

M Stoll, U M Steckelings, M Paul, S P Bottari, R Metzger, T Unger

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 1998 1997 1996 1995 Total
Citations: 1 5 2 4 4 2 5 3 5 3 12 4 9 15 16 25 16 18 16 16 29 28 30 39 54 50 69 61 54 45 11 651
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Citations to this article in year 2001 (54)

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Transgenic mouse models of angiotensin receptor subtype function in the cardiovascular system
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Angiotensin II type 2 receptor inhibits epidermal growth factor receptor transactivation by increasing association of SHP-1 tyrosine phosphatase
Y Shibasaki, H Matsubara, Y Nozawa, Y Mori, H Masaki, A Kosaki, Y Tsutsumi, Y Uchiyama, S Fujiyama, A Nose, O Iba, E Tateishi, T Hasegawa, M Horiuchi, C Nahmias, T Iwasaka
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