Abstract 1898: Ischemic Preconditioning Enhances the Mobilization and Recruitment of Bone Marrow Stem Cells to Protect Against Ischemia/Reperfusion Injury in the Late Phase
It is known that cardioprotection against ischemia/reperfusion (I/R) injury occurs in the late phase after ischemic preconditioning (IPC), but the precise mechanism is unclear. We investigated if the mobilization and recruitment of bone marrow-derived progenitor cells contribute to cardioprotection in the late phase of IPC. IPC was created with four cycles of 5-min occlusion and reperfusion of the abdominal aorta in mice. Heart I/R injury was induced by occluding the left anterior descending artery for 30 min, immediately (early phase) or 24 h (late phase) after IPC. Serum VEGF and SDF-1α levels were increased significantly 1 and 3 h after IPC in comparison with control, but bone marrow-derived CD34+ and CD34+/flk-1+ stem cells in the peripheral blood were increased significantly 24 h after IPC (Figure 1⇓). Compared with the control treatment, both the early and late phases of IPC protected the heart against I/R injury by inhibiting cardiomyocyte apoptosis (1.7±0.5 and 2.0±1.1 cells/103 nuclei vs 7.3±1.9 cells/103 nuclei, P<0.001) and increasing left ventricular fractional shortening (48.6±3.9% and 44.6±3.6% vs 30.9±4.1%, P<0.0001). However, the recruitment of bone marrow-derived Sca-1+ stem cells was significantly greater in the heart when I/R injury was induced in late phase than in the early phase of IPC (2.7±0.5 vs 1.40.1, P<0.001). Cardioprotection against I/R injury was observed in the early and late phases of IPC; however, the enhanced mobilization and recruitment of bone marrow-derived stem cells played an important role in protecting the heart against I/R injury in the late phase of IPC.