Human Endothelial Progenitor Cells Tolerate Oxidative Stress Due to Intrinsically High Expression of Manganese Superoxide Dismutase

Abstract

Objective— Endothelial progenitor cells (EPCs) display a unique aptitude to promote angiogenesis and restore endothelial function of injured vessels. How progenitor cells can execute a regenerative program in the unfavorable environment of injury/inflammation-induced oxidative stress is poorly understood. We hypothesized that EPCs are resistant to oxidative stress and that this resistance is due to high expression and activity of antioxidant enzymes. Methods and Results— EPCs outgrown from human blood of healthy subjects demonstrated a marked resistance to cytotoxic effect of LY83583 (an generator), tumor necrosis factor-α, and serum depletion. LY83583 inhibited in vitro tube formation by human umbilical vein endothelial cells (HUVECs) and human coronary artery endothelial cells (CAECs), but not by EPCs. Compared with HUVECs and CAECs, EPCs exhibited ≈3- to 4-fold higher expression and activity of manganese superoxide dismutase (MnSOD), but not copper zinc superoxide dismutase (CuZnSOD) or catalase. The a... We provide evidence that human endothelial progenitor cells (EPCs) are resistant to oxidative stress imposed by induced concentration of superoxide anions. Analysis of this phenomenon demonstrated that high intrinsic expression of manganese superoxide dismutase in EPCs is a critical mechanism underlying EPCs resistance to oxidative stress.