Beneficial Effects of Angiotensin (1–7) On Dysfunctional CD34+ Endothelial Progenitor Cells (EPC) from Patients with Heart Failure

Endothelial dysfunction is well established in heart failure (HF) and thus HF individuals can be benefitted from autologous cell therapy. In HF patients, the numbers of circulating EPCs vary with NYHA stage. We hypothesized that CD34 + EPCs are dysfunctional in heart failure (HF) patients which can be corrected by angiotensin 1–7 (Ang‐(1–7)). Peripheral blood was collected from control (n=10) and NYHA class II‐IV HF patients (n=15). CD34 + cells were enumerated by flow cytometry and were assessed for migratory potential, NO generation, ROS levels with and without Ang1–7. HF patients showed 63% reduction in number of CD34 + cells, 60% reduction in BFU‐E, 74% increase in CFU‐GEMM colonies, reduced expression of ACE2, MAS1 and IL‐10 whereas increased expression of TNF‐α and IL‐6 compared to controls. Migratory potential of CD34 + cells in HF patients were reduced by 77%. Additionally, CD34 + cells from class III donors had 44% reduction in NO/ROS ratio due to increased ROS and reduced NO. Ang‐(1–7) treatment improved their migratory response, reduced ROS and increased NO which resulted in a 54% increase in NO/ROS ratio. These data support that CD34 + cells isolated from HF individuals are dysfunctional, with a reduction in number, colony forming ability, migratory potential, NO generation and increased oxidative stress and these dysfunctions can be corrected by Ang‐(1–7), which suggests therapeutic potential of Ang‐(1–7). This work was supported by HL56921