- 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.