Abstract 17052: Concomitant Overexpression of Sod1, Sod3, and Gshpx-1 Improves Recovery of the Ischemic Limb in Mice Independent of Endothelial Progenitor Cell Mobilization
Oxidative stress plays an important role in ischemic injury. Limb ischemia is a potent stimulator for endothelial progenitor cell (EPC) mobilization. The present study was to determine if concomitant overexpression of SOD1, SOD3, and glutathione peroxidase (GSHPx)-1 could enhance EPC mobilization and the recovery of ischemic limb following ischemic injury. Hind limb ischemia was created with ligation of the right femoral artery in male tripletransgenic mice that overexpressed human SOD1, SOD3, and GSHPx-1 with C57BL6 background (transgenic mice) and littermate wild-type male C57BL6 (control mice). The limb blood flow as measured using a Doppler flowmeter in the transgenic mice recovered significantly faster than that in the control mice. The function recovery as reflected by treadmill exercise time was much faster in the transgenic animals compared to the controls. Circulating EPC level was similar in the two animal groups at baseline as determined using flowcytometry (cells were considered EPCs when positive for both Sca-1 and Flk-1 or c-Kit and CD31 or CD34 and Flk-1). Circulating EPC levels were significantly increased in the setting of ischemia in the mice of both groups. However, there was no significant difference in the EPC level in the two groups of mice. Intracellular production of reactive oxygen species (ROS) was significantly reduced in the transgenic mice as expected. Interestingly, the levels of phosphorylated Akt and ERK1/2 were significantly increased in the limb muscle in the transgenic mice over the control. These data demonstrated that concomitant overexpression of SOD1, SOD3, and GSHPx-1 significantly promoted recovery of the ischemic limb independent of EPC mobilization in the mice. The beneficial effects might be related to increased Akt and/or ERK1/2 signaling or decreased ROS production in the mice overexpressing SOD1, SOD3, and GSHPx-1.
- © 2013 by American Heart Association, Inc.