Abstract 16185: Ang-(1-7) Corrects CD34+ Endothelial Progenitor Cell (EPC) Dysfunction from Patients with Heart Failure
Introduction: Circulating EPC numbers are reduced in patients with cardiovascular disease (CVD) however, less is known about the functional capabilities and reparative potential of these cells. The primary function of EPCs is to migrate to areas of ischemic injury to repair and they home towards hypoxia- regulated factor such as stromal cell-derived factor (SDF-1α). Their migration is dependent on nitric oxide (NO) bioavailability and is adversely impacted by oxidative stress. Hypothesis: We hypothesized that the CD34+ EPCs dysfunction is dependent on the stage of heart failure (HF) and CD34+ EPCs dysfunction can be corrected by angiotensin 1-7 (Ang-(1-7)) as Ang-(1-7) has been shown to reduce oxidative stress and increase nitric oxide synthase.
Methods: Peripheral blood was collected from control (n=8) and HF patients (n=8) with the inclusion criteria of significant coronary artery disease, greater than 70% luminal diameter narrowing of at least one major coronary artery, LVEF<45% limiting angina (class II to IV) and/or congestive heart failure (NYHA class II-III). The patients studied were categorized under NYHA class II and class III. CD34+ cells were isolated by immune-magnetic separation technique and assessed for migratory potential (modified Boyden Chamber assay), nitric oxide (NO) generation in response to SDF-1 and Ang1-7 (measuring DAF-FM fluorescence), and reactive oxygen species (ROS) levels (measuring dihydroethidium (DHE) fluorescence).
Results: The migratory potential of CD34+ cells in HF patients were reduced by 65% compared to controls (*p<0.01), with most reduction (74%, *p<0.01) in NYHA class III. Furthermore, CD34+ cells isolated from NYHA class III donors had significant reduction in NO (*p<0.001) and an increase in ROS (*p<0.05) compared to control CD34+ cells. Treatment of CD34+ cells from HF patients with 100nM Ang-(1-7) resulted in reduction in ROS (*p<0.05) and an increase in NO (*p<0.01).
Conclusions: These data support that CD34+ cells isolated from HF patients have reduced migratory potential, reduced NO, and increased oxidative stress and that this dysfunction can be corrected by Ang-(1-7), suggesting the therapeutic potential of Ang-(1-7) in this patient population.
- © 2012 by American Heart Association, Inc.