Abstract 14786: Angiotensin (1-7) Counteracting the Effects of Angiotensin II in Regulating Endothelial Progenitor Cell Function Through eNOS/NO, Nox/ROS And SDF-1α/CXCR4 Pathways
Our previous study has shown that bone marrow (BM) derived endothelial progenitor cells (EPCs) are dysfunctional in the human rennin and angiotensinogen double transgenic (R+A+) mice. In this study, we investigated the role of angiotensin (1-7) [Ang (1-7)] in modulating the function of EPCs and the underlying mechanisms. BM derived-EPCs cultured from R+A+ mice were divided into five treatment groups (n=8/group): control (basal medium), 10-7 mmol/L Ang (1-7) alone or with A-779 (Mas antagonist, 10-7 mmol/L) or with apocynin (Nox inhibitor, 10 µmol/L) or with L-NAME (eNOS inhibitor, 1 mmol/L). EPC functions (migration and tube formation) were evaluated using the Boyden chamber and the kit for tube formation assay. The levels of stromal cell-derived factor-1α (SDF-1α), CXC chemokine receptor 4 (CXCR4), endothelial nitric oxide synthase (eNOS) and NADPH oxidase subunits (Nox2, 4) were measured by Western blot. Reactive oxygen species (ROS) and nitric oxide (NO) production was determined by dihydroethidium staining and 4, 5-diaminofluorescein method, respectively. We found (Table): 1) Adding Ang (1-7) to the culture medium improved the compromised migration and tube formation abilities of EPCs derived from the R+A+ mice. 2) Treatment with Ang (1-7) was associated with up-regulation of eNOS and SDF-1α/CXCR4 proteins, and down-regulation of Nox2, 4 proteins, as well as consequential NO and NOS production in EPCs. 3) These effects of Ang (1-7) induced were able to be totally abolished by A-799, partially inhibited by L-NAME, and partially enhanced by apocynin. In conclusion, our data demonstrate that Ang (1-7) counteracts Ang II in regulating EPC function via Mas receptors and the downstream eNOS, Nox and CXCR4 pathways.
- © 2012 by American Heart Association, Inc.