Abstract 557: ACE2/Angiotensin-(1-7) Stimulates Vasoprotection-Relevant Functions of Human CD34+ Cells
Angiotensin converting enzyme 2 (ACE2) and angiotensin (Ang)-(1-7), key members of the vasoprotective axis of the renin-angiotensin system (RAS), have been shown to modulate hematopoietic functions of bone marrow-derived cells. This coupled with recent studies implicating the involvement of bone marrow stem/progenitor cells in the cardiovascular functions, we evaluated the expression of RAS components and functions of ACE2 and Ang-(1-7) in human CD34+ cells, hematopoietic stem cells with vasoprotective functions.
Peripheral blood was obtained from healthy individuals and CD34+ cells were isolated by immunomagnetic separation. Real-time PCR was carried out, and the effects of Ang II, Ang-(1-7), NorLeu3Ang-(1-7), and ACE2 activators, diminazene aceturate (DIZI) and a xanthenone derivative (XNT), were evaluated on migration, proliferation and adhesion of CD34+ cells. Paracrine factors produced by CD34+ cells were analyzed. CD34+ cells showed the presence of mRNA transcripts of ACE, ACE2 and Mas1 receptor. In contrast, renin, angiotensinogen, and AT1 and AT2 receptors were not detectable. Treatment with 100nM Ang-(1-7) or 10nM NorLeu3Ang-(1-7) stimulated proliferation and migration of CD34+ cells while adhesion of these cells to fibronectin was not affected. Ang-(1-7) treatment altered the paracrine profile of CD34+ cells: increased
IL10, IL8, G-CSF, GM-CSF, IGFBP-3 and decorin (P<0.03), and decreased IGF1, thrombopoietin and TGFβ1 levels (P<0.05, n=5). In contrast, 100nM Ang II has no effects on proliferation and migration of CD34+ cells. However, in the presence of Ang II, 100nM DIZI or 100nM XNT increased proliferation and migration of CD34+ cells compared to the cells treated with Ang II alone (P<0.05, n=7). Treatment of total leucocytes with Ang II prior to the isolation of CD34+ cells attenuated their migration to stromal-derived factor-1α and proliferation compared to the untreated (P<0.05, n=5), and enhanced their adhesion to fibronectin. These studies suggest that activation of endogenous ACE2 or treatment with Ang-(1-7) stimulates the functions of CD34+ cells that are indicators of their cardiovascular protective functions while Ang II may attenuate these properties indirectly via acting on leucocytes.
Author Disclosures: N. Singh: None. L. Guo: None. N. Alberto: None. S.B. Bartelmez: None. M.K. Raizada: None. Y.P. Jarajapu: None.
This research has received full or partial funding support from the American Heart Association.
- © 2014 by American Heart Association, Inc.