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Angiotensin‐(1–7) treatment ameliorates angiotensin II ‐induced apoptosis of human umbilical vein endothelial cells
Author(s) -
Yang HuiYu,
Bian YunFei,
Zhang HuaPing,
Gao Fen,
Xiao ChuanShi,
Liang Bin,
Li Jin,
Zhang NaNa,
Yang ZhiMing
Publication year - 2012
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12016
Subject(s) - umbilical vein , angiotensin ii , apoptosis , renin–angiotensin system , human umbilical vein endothelial cell , angiotensin 1 , chemistry , pharmacology , medicine , endocrinology , biochemistry , receptor , blood pressure , in vitro
Summary Angiotensin (Ang)‐(1–7), a metabolite of Ang I and Ang II , is a counter‐regulatory mediator of Ang II . In the present study, we investigated the effects of Ang‐(1–7) on Ang II ‐induced apoptosis in human umbilical vein endothelial cells ( HUVEC ). To this end, HUVEC were pretreated with 10 −9 , 10 −8 , 10 −7 or 10 −6 mol/L Ang‐(1–7) at for 30 min before being stimulated with 10 −6 mol/L Ang‐ II for another 24 h. Acridine orange/ethidium bromide and propidium iodide staining were used to analyse the effects of Ang‐(1–7) on Ang II ‐induced apoptosis. Alone, 10 −6 mol/L Ang‐(1–7) had no effect on the apoptosis of HUVEC following exposure of cells for 30 min, whereas Ang II (10 −6 mol/L, 24 h) significantly enhanced the number of apoptotic cells ( P < 0.01). The Ang II ‐induced apoptosis of HUVEC was suppressed by 10 −9 –10 −6 mol/L Ang‐(1–7). The anti‐apoptotic effects of Ang‐(1–7) were almost completely abolished by A‐779 (10 −6 mol/L, 30 min), a specific Mas receptor antagonist. In addition, Ang‐(1–7) inhibited Ang II ‐induced accumulation of cleaved caspase 3 and enhanced the expression of the anti‐apoptotic factor Bcl‐2 at both the mRNA and protein levels. Angiotensin II upregulated the expression of lectin‐like oxidized low‐density lipoprotein receptor‐1 ( LOX ‐1), which is involved in endothelial apoptosis, at both the mRNA and protein levels. This effect was blocked by Ang‐(1–7) in a concentration‐dependent manner, although A‐779 almost completely reversed Ang‐(1–7)‐mediated inhibition of Ang II ‐induced upregulation of LOX ‐1. Silencing of LOX ‐1 using short interference RNA enhanced the protective effects of Ang‐(1–7) against Ang II ‐induced apoptosis in HUVEC . Together, the results suggest that Ang‐(1–7) ameliorates Ang II ‐induced apoptosis of HUVEC at least in part by suppressing LOX ‐1 expression.