Korean Circulation Journal

The Korean Society of Cardiology (대한심장학회)
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Cardioprotective Effect of the SDF-1α/CXCR4 Axis in Ischemic Postconditioning in Isolated Rat Hearts

  • Kim, Jeong Su (Cardiovascular Research Institute, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital) ;
  • Jang, Youngho (Cardiovascular Research Institute, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital) ;
  • Kim, June Hong (Cardiovascular Research Institute, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital) ;
  • Park, Yong Hyun (Cardiovascular Research Institute, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital) ;
  • Hwang, Sun Ae (Cardiovascular Research Institute, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital) ;
  • Kim, Jun (Asan Medical Center, University of Ulsan College of Medicine) ;
  • Lee, Sung-Ryul (National Research Laboratory for Mitochondrial Signaling, Department of Physiology, Inje University College of Medicine) ;
  • Xu, Zhelong (Department of Anesthesiology, University of North Carolina) ;
  • Ban, Changill (Department of Chemistry, Pohang University of Science and Technology) ;
  • Ahn, Kyohan (Department of Chemistry, Pohang University of Science and Technology) ;
  • Chun, Kook Jin (Cardiovascular Research Institute, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital)
  • Received : 2016.09.29
  • Accepted : 2017.08.06
  • Published : 2017.11.30
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Abstract

Background and Objectives: Information about the role of the stromal cell-derived factor-$1{\alpha}$ ($SDF-1{\alpha}$)/chemokine receptor type 4 (CXCR4) axis in ischemic postconditioning (IPOC) is currently limited. We hypothesized that the $SDF-1{\alpha}$/CXCR4 signaling pathway is directly involved in the cardioprotective effect of IPOC. Methods: Isolated rat hearts were divided into four groups. The control group was subjected to 30-min of regional ischemia and 2-hour of reperfusion (n=12). The IPOC group was induced with 6 cycles of 10-second reperfusion and 10-second global ischemia (n=8) in each cycle. The CXCR4 antagonist, AMD3100, was applied before reperfusion in the IPOC group (AMD+IPOC group, n=11) and control group (AMD group, n=9). Hemodynamic changes with electrocardiography were monitored and infarct size was measured. The $SDF-1{\alpha}$, lactate dehydrogenase (LDH) and creatine kinase (CK) concentrations in perfusate were measured. We also analyzed extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt phosphorylation state expression. Results: IPOC significantly reduced infarct size, but AMD3100 attenuated the infarct reducing effect of IPOC. IPOC significantly decreased LDH and CK, but these effects were reversed by AMD3100. ERK1/2 and Akt phosphorylation increased with IPOC and these effects were blocked by AMD3100. Conclusion: Based on the results of this study, $SDF-1{\alpha}$/CXCR4 signaling may be involved in IPOC cardioprotection and this signaling pathway couples to the ERK1/2 and Akt pathways.

Keywords

Acknowledgement

Supported by : Pusan National University Yangsan Hospital

References

  1. Kin H, Zhao ZQ, Sun HY, et al. Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion. Cardiovasc Res 2004;62:74-85. https://doi.org/10.1016/j.cardiores.2004.01.006
  2. Tsang A, Hausenloy DJ, Mocanu MM, Yellon DM. Postconditioning: a form of "modified reperfusion" protects the myocardium by activating the phosphatidylinositol 3-kinase-Akt pathway. Circ Res 2004;95:230-2. https://doi.org/10.1161/01.RES.0000138303.76488.fe
  3. Darling CE, Jiang R, Maynard M, Whittaker P, Vinten-Johansen J, Przyklenk K. Postconditioning via stuttering reperfusion limits myocardial infarct size in rabbit hearts: role of ERK1/2. Am J Physiol Heart Circ Physiol 2005;289:H1618-26. https://doi.org/10.1152/ajpheart.00055.2005
  4. Hausenloy DJ, Tsang A, Yellon DM. The reperfusion injury salvage kinase pathway: a common target for both ischemic preconditioning and postconditioning. Trends Cardiovasc Med 2005;15:69-75. https://doi.org/10.1016/j.tcm.2005.03.001
  5. Jang Y, Xi J, Wang H, Mueller RA, Norfleet EA, Xu Z. Postconditioning prevents reperfusion injury by activating delta-opioid receptors. Anesthesiology 2008;108:243-50. https://doi.org/10.1097/01.anes.0000299437.93898.4a
  6. Mykytenko J, Reeves JG, Kin H, et al. Persistent beneficial effect of postconditioning against infarct size: role of mitochondrial K(ATP) channels during reperfusion. Basic Res Cardiol 2008;103:472-84. https://doi.org/10.1007/s00395-008-0731-2
  7. Abbott JD, Huang Y, Liu D, Hickey R, Krause DS, Giordano FJ. Stromal cell-derived factor-1alpha plays a critical role in stem cell recruitment to the heart after myocardial infarction but is not sufficient to induce homing in the absence of injury. Circulation 2004;110:3300-5. https://doi.org/10.1161/01.CIR.0000147780.30124.CF
  8. Askari AT, Unzek S, Popovic ZB, et al. Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy. Lancet 2003;362:697-703. https://doi.org/10.1016/S0140-6736(03)14232-8
  9. Hu X, Dai S, Wu WJ, et al. Stromal cell derived factor-1 alpha confers protection against myocardial ischemia/reperfusion injury: role of the cardiac stromal cell derived factor-1 alpha CXCR4 axis. Circulation 2007;116:654-63. https://doi.org/10.1161/CIRCULATIONAHA.106.672451
  10. Huang C, Gu H, Zhang W, Manukyan MC, Shou W, Wang M. SDF-1/CXCR4 mediates acute protection of cardiac function through myocardial STAT3 signaling following global ischemia/reperfusion injury. Am J Physiol Heart Circ Physiol 2011;301:H1496-505. https://doi.org/10.1152/ajpheart.00365.2011
  11. Jang YH, Kim JH, Ban C, et al. Stromal cell derived factor-1 (SDF-1) targeting reperfusion reduces myocardial infarction in isolated rat hearts. Cardiovasc Ther 2012;30:264-72. https://doi.org/10.1111/j.1755-5922.2011.00301.x
  12. van Vuuren D, Genis A, Genade S, Lochner A. Postconditioning the isolated working rat heart. Cardiovasc Drugs Ther 2008;22:391-7. https://doi.org/10.1007/s10557-008-6119-6
  13. Tachibana K, Hirota S, Iizasa H, et al. The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract. Nature 1998;393:591-4. https://doi.org/10.1038/31261
  14. Wei YJ, Tang Y, Li J, et al. Cloning and expression pattern of dog SDF-1 and the implications of altered expression of SDF-1 in ischemic myocardium. Cytokine 2007;40:52-9. https://doi.org/10.1016/j.cyto.2007.08.004
  15. Segret A, Rucker-Martin C, Pavoine C, et al. Structural localization and expression of CXCL12 and CXCR4 in rat heart and isolated cardiac myocytes. J Histochem Cytochem 2007;55:141-50. https://doi.org/10.1369/jhc.6A7050.2006
  16. Hausenloy DJ, Yellon DM. Survival kinases in ischemic preconditioning and postconditioning. Cardiovasc Res 2006;70:240-53. https://doi.org/10.1016/j.cardiores.2006.01.017
  17. Zhu M, Feng J, Lucchinetti E, et al. Ischemic postconditioning protects remodeled myocardium via the PI3K-PKB/Akt reperfusion injury salvage kinase pathway. Cardiovasc Res 2006;72:152-62. https://doi.org/10.1016/j.cardiores.2006.06.027
  18. Yang XM, Proctor JB, Cui L, Krieg T, Downey JM, Cohen MV. Multiple, brief coronary occlusions during early reperfusion protect rabbit hearts by targeting cell signaling pathways. J Am Coll Cardiol 2004;44:1103-10. https://doi.org/10.1016/j.jacc.2004.05.060
  19. Jujo K, Hamada H, Iwakura A, et al. CXCR4 blockade augments bone marrow progenitor cell recruitment to the neovasculature and reduces mortality after myocardial infarction. Proc Natl Acad Sci U S A 2010;107:11008-13. https://doi.org/10.1073/pnas.0914248107
  20. Chen Z, Li T, Zhang B. Morphine postconditioning protects against reperfusion injury in the isolated rat hearts. J Surg Res 2008;145:287-94. https://doi.org/10.1016/j.jss.2007.07.020
  21. Methner C, Schmidt K, Cohen MV, Downey JM, Krieg T. Both A2a and A2b adenosine receptors at reperfusion are necessary to reduce infarct size in mouse hearts. Am J Physiol Heart Circ Physiol 2010;299:H1262-4. https://doi.org/10.1152/ajpheart.00181.2010
  22. Peart JN, Gross GJ. Adenosine and opioid receptor-mediated cardioprotection in the rat: evidence for cross-talk between receptors. Am J Physiol Heart Circ Physiol 2003;285:H81-9. https://doi.org/10.1152/ajpheart.00985.2002