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PRE-CLINICAL RESEARCH

Ischemic Pre-Conditioning Enhances the Mobilization and Recruitment of Bone Marrow Stem Cells to Protect Against Ischemia/Reperfusion Injury in the Late Phase

Department of Surgery and Clinical Science, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan

Manuscript received September 30, 2008; revised manuscript received February 10, 2009, accepted February 16, 2009.

^_* Reprint requests and correspondence: Dr. Tao-Sheng Li, Department of Surgery and Clinical Science, Yamaguchi University, Graduate School of Medicine, 1-1-1 Minami Kogushi, Ube, Yamaguchi 755-8505, Japan (Email: litaoshe{at}yamaguchi-u.ac.jp).

Objectives: The aim of this study was to investigate whether the mobilization and recruitment of bone marrow stem cells (BMSCs) contribute to cardioprotection in the late phase after ischemic pre-conditioning (IPC).

Background: IPC is an innate phenomenon in which brief exposure to sublethal ischemia provides tissue protection from subsequent ischemia/reperfusion (I/R) injury. A delayed cardioprotection also occurs after IPC, but the precise mechanism is unclear.

Methods: IPC was created with 4 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.

Results: Serum vascular endothelial growth factor and stromal cell-derived factor-1 levels were increased significantly 1 and 3 h after IPC, but CD34+ and CD34+/flk-1+ stem cells in the peripheral blood were increased significantly 12 and 24 h after IPC (p < 0.05). Compared with the control treatment, both the early and late phases of IPC protected the heart against I/R injury. However, the recruitment of BMSCs was significantly greater in the heart when I/R injury was induced in late phase than in the early phase of IPC (p < 0.01). Interestingly, the blockade of the recruitment of BMSCs significantly attenuated the cardioprotective effect of IPC in the late phase (p < 0.01) but did not change in the early phase.

Conclusions: Cardioprotection was observed in the early and late phases of IPC; however, the enhanced mobilization and recruitment of BMSCs played an important role in the late phase of IPC.

Key Words: bone marrow stem cell • ischemic pre-conditioning • late phase • mobilization • recruitment

Abbreviations and Acronyms   BMSC = bone marrow stem cell   BMT = bone marrow transplantation   GFP = green fluorescent protein   IPC = ischemic pre-conditioning   I/R = ischemia/reperfusion   LV = left ventricle/ventricular   LVEDD = left ventricular end-diastolic diameter   LVESD = left ventricular end-systolic diameter   LVFS = left ventricular fractional shortening   SDF = stromal cell-derived factor   TUNEL = terminal deoxynucleotidyl transferase dUTP nick end labeling   VE = vascular endothelial   VEGF = vascular endothelial growth factor

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J. Am. Coll. Cardiol. 2009 53: A30. [Full Text] [PDF]