Angiotensin (Ang)‐(1–7), a metabolite of AngI and AngII, is a counter‐regulatory mediator of AngII. In the present study,
we investigated the effects of Ang‐(1–7) on AngII‐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 AngII‐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 AngII (10−6 mol/L, 24 h) significantly enhanced the number of apoptotic cells (P < 0.01).
The AngII‐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 AngII‐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 AngII‐induced upregulation of LOX‐1. Silencing of LOX‐1 using short interference RNA enhanced
the protective effects of Ang‐(1–7) against AngII‐induced apoptosis in HUVEC. Together, the results suggest that Ang‐(1–7) ameliorates AngII‐induced apoptosis of HUVEC at least in part by suppressing LOX‐1 expression.
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Document Type: Research Article
Publication date: December 1, 2012