Abstract 1554: The Altered Response of Bone Marrow Derived Endothelial Progenitor Cells from Normal and Heart Failure Rats to Angiotensin-(1–7)
Background: Angiotensin-(1–7) [Ang-(1–7)] attenuates in-stent restenosis and improves endothelial function. Endothelial progenitor cells (EPCs) have been implicated in cardiovascular repair. We hypothesized that EPC provides a target for the beneficial effect of Ang-(1–7). Therefore, we studied the effect of Ang-(1–7) on EPCs from normal and heart failure rats.
Methods: Mononuclear cells were isolated from rat bone marrow or blood. After 2 days of culture, the cells were treated for 7 days with cumulative doses of Ang-(1–7) (from 10−11M to 10−7M), in absence or presence of antagonists for the mas receptor (A779,10−7M), the AT1 receptor ( Losartan,10−7M), or the AT2 receptor (PD123.319 10-7M). Thereafter, EPCs were quantified by nuclear staining with DAPI, up-taking Dil-Ac-LDL and BSI lectin binding.
Results: Bone marrow-derived EPCs from normal rats were dose-dependently increased by Ang-(1–7), which was totally blocked by A779 or Losartan (see figure⇓). Moreover, Ang-(1–7) increased bone marrow- and blood-derived EPC from sham rats by 350% and 55% above baseline (p<0.05, n=5), respectively. These effects were totally inhibited by A779. In heart failure rats, the response of EPC to Ang-(1–7) was blunted. Bone marrow- and blood-derived EPCs were stimulated up to 100 % and 20% above baseline, respectively (p<0.05, n=5). Interestingly, a loss of sensitivity to A779 was observed from bone marrow of heart failure rats.
Ang-(1–7) increases EPC differentiation by Mas or AT1 receptor.
The response of EPCs from heart failure rats to Ang-(1–7) is decreased, which might indicate a loss of beneficial repair mechanism of Ang-(1–7) in long-term heart failure.