Abstract: Objective To observe the expression changes of microRNA 1 (miRNA-1) and microRNA 21(miRNA-21) after ischemic preconditioning (IPC), ischemic postconditioning (IPO) and remote ischemic preconditioning (RIPC)in an ischemia-reperfusion rat heart model in vitro, as well as the expression of their target protein heat shock protein 70 (HSP70) and programmed cell death 4 (PDCD4), and evaluate whether miRNA are involved in endogenous cardio-protective mechanism. Methods The Langendorff-perfused Sprague-Dawley rat hearts were randomly assigned into one of the four groups, control group (CON group, n=12), ischemia preconditioning group (IPC group, n=12) , ischemia postconditioning group (IPO group, n=12) and remote ischemia preconditioning group (RIPC group,n=12). Cardiac function was digitalized and analyzed. The expression of HSP70, PDCD4, B-cell lymphoma/leukemia-2 (Bcl-2) and Bax was detected by Western blotting. The expression of miRNA-1 and miRNA-21 was detected by real-time reverse transcriotion-polymerase chain reaction (RT-PCR). Assessment of cardiac infarct size and myocardial apoptosis was determined using triphenyltetrazolium chloride (TTC) assay and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) assay respectively. Results The expressions of miRNA-1 and miRNA-21 were up-regulated in IPC group, but the expression of miRNA-1 was down-regulated in RIPC group and IPO group (P<0.05). The expressionsof PDCD4, HSP70 and Bax were down-regulated in ‘conditioning’ groups compared with CON group (P<0.05). The expression of Bcl-2 was not statistically different among the four groups. The infarct size and the myocardial apoptosis in ‘conditioning’ hearts were significantly decreased compared with CON group (P<0.05). Conclusion The expressions of the miRNA-1 and miRNA-21 are different in IPC, RIPC and IPO groups, and their target proteins are not inversely correlated with the miRNAs in all the ‘conditioning’ groups.
Citation:
DUAN Xin,WANG Xiaohua,JI Bingyang,LIU Jinping,LONG Cun.. Expression of MicroRNA-1, 21 in Ischemic Preconditioning, Ischemic Postconditioning and Remote Ischemic Preconditioning in an Isolated Rat Heart Model. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2012, 19(4): 402-406. doi:
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Cardiovasc Res, 2001,51 (4):637-646.
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Hausenloy DJ, Yellon DM. The evolving story of “conditioning” to protect against acute myocardial ischaemia-reperfusion injury. Heart, 2007, 93 (6):649-651.
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Zhao ZQ, Corvera JS, Halkos ME, et al. Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning. Am J Physiol Heart Circ Physiol, 2003, 285 (2):H579-588.
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Przyklenk K, Bauer B, Ovize M, et al. Regional ischemic ′preconditioning′ protects remote virgin myocardium from subsequent sustained coronary occlusion. Circulation, 1993, 87 (3):893-899.
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Gho BC, Schoemaker RG, van den Doel MA, et al. Myocardial protection by brief ischemia in noncardiac tissue. Circulation, 1996, 94 (9):2193-2200.
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Pell TJ, Baxter GF, Yellon DM, et al. Renal ischemia preconditions myocardium:role of adenosine receptors and ATP-sensitive potassium channels. Am J Physiol, 1998, 275 (5 Pt 2):H1542-1547.
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Kharbanda RK, Mortensen UM, White PA, et al. Transient limb ischemia induces remote ischemic preconditioning in vivo.Circulation, 2002,106 (23):2881-2883.
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Bushati N, Cohen SM. microRNA functions. Annu Rev Cell Dev Biol, 2007, 23 (1):175-205.
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Chang TC, Mendell JT. microRNAs in vertebrate physiology and human disease. Annu Rev Genomics Hum Genet, 2007, 8:215-239.
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Yin C, Salloum FN, Kukreja RC. A novel role of microRNA in late preconditioning: upregulation of endothelial nitric oxide synthase and heat shock protein 70. Circ Res, 2009,104 (5):572-575.
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12. |
Cheng Y, Zhu P, Yang J, et al. Ischaemic preconditioning-regulated miR-21 protects heart against ischaemia/reperfusion injury via anti-apoptosis through its target PDCD4. Cardiovasc Res,87 (3):431-439.
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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 (2):69-75.
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14. |
Wang Y, Xu H, Mizoguchi K, et al. Intestinal ischemia induces late preconditioning against myocardial infarction: a role for inducible nitric oxide synthase. Cardiovasc Res, 2001,49 (2):391-398.
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15. |
Kuntscher MV, Kastell T, Altmann J, et al. Acute remote ischemic preconditioning II: the role of nitric oxide. Microsurgery, 2002,22 (6):227-231.
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16. |
Xu C, Lu Y, Pan Z, et al. The muscle-specific microRNAs miR-1 and miR-133 produce opposing effects on apoptosis by targeting HSP60, HSP70 and caspase-9 in cardiomyocytes. J Cell Sci, 2007,120 (Pt 17):3045-3052.
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Kwon C, Han Z, Olson EN, et al. MicroRNA1 influences cardiac differentiation in Drosophila and regulates Notch signaling. Proc Natl Acad Sci U S A, 2005,102 (52):18986-18991.
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Chen JF, Mandel EM, Thomson JM, et al. The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat Genet, 2006,38 (2):228-233.
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Heusch G, Boengler K, Schulz R. Cardioprotection: nitric oxide, protein kinases, and mitochondria. Circulation, 2008,118 (19):1915-1919.
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Latchman DS. Heat shock proteins and cardiac protection.
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Hampton CR, Shimamoto A, Rothnie CL, et al. HSP70.1 and -70.3 are required for late-phase protection induced by ischemic preconditioning of mouse hearts. Am J Physiol Heart Circ Physiol, 2003,285 (2):H866-874.
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22. |
Wang G, Liem DA, Vondriska TM, et al. Nitric oxide donors protect murine myocardium against infarction via modulation of mitochondrial permeability transition. Am J Physiol Heart Circ Physiol, 2005,288 (3):H1290-1295.
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Precht TA, Phelps RA, Linseman DA, et al. The permeability transition pore triggers Bax translocation to mitochondria during neuronal apoptosis. Cell Death Differ, 2005,12 (3):255-265.
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Schmitt JP, Schroder J, Schunkert H, et al. Role of apoptosis in myocardial stunning after open heart surgery. Ann Thorac Surg, 2002,73 (4):1229-1235.
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Penna C, Tullio F, Merlino A, et al. Postconditioning cardioprotection against infarct size and post-ischemic systolic dysfunction is influenced by gender. Basic Res Cardiol, 2009,104 (4):390-402.
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- 1. Cardiovasc Res, 2001,51 (4):637-646.
- 2. Hausenloy DJ, Yellon DM. The evolving story of “conditioning” to protect against acute myocardial ischaemia-reperfusion injury. Heart, 2007, 93 (6):649-651.
- 3. Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation, 1986, 74 (5):1124-1136.
- 4. Zhao ZQ, Corvera JS, Halkos ME, et al. Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning. Am J Physiol Heart Circ Physiol, 2003, 285 (2):H579-588.
- 5. Przyklenk K, Bauer B, Ovize M, et al. Regional ischemic ′preconditioning′ protects remote virgin myocardium from subsequent sustained coronary occlusion. Circulation, 1993, 87 (3):893-899.
- 6. Gho BC, Schoemaker RG, van den Doel MA, et al. Myocardial protection by brief ischemia in noncardiac tissue. Circulation, 1996, 94 (9):2193-2200.
- 7. Pell TJ, Baxter GF, Yellon DM, et al. Renal ischemia preconditions myocardium:role of adenosine receptors and ATP-sensitive potassium channels. Am J Physiol, 1998, 275 (5 Pt 2):H1542-1547.
- 8. Kharbanda RK, Mortensen UM, White PA, et al. Transient limb ischemia induces remote ischemic preconditioning in vivo.Circulation, 2002,106 (23):2881-2883.
- 9. Bushati N, Cohen SM. microRNA functions. Annu Rev Cell Dev Biol, 2007, 23 (1):175-205.
- 10. Chang TC, Mendell JT. microRNAs in vertebrate physiology and human disease. Annu Rev Genomics Hum Genet, 2007, 8:215-239.
- 11. Yin C, Salloum FN, Kukreja RC. A novel role of microRNA in late preconditioning: upregulation of endothelial nitric oxide synthase and heat shock protein 70. Circ Res, 2009,104 (5):572-575.
- 12. Cheng Y, Zhu P, Yang J, et al. Ischaemic preconditioning-regulated miR-21 protects heart against ischaemia/reperfusion injury via anti-apoptosis through its target PDCD4. Cardiovasc Res,87 (3):431-439.
- 13. 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 (2):69-75.
- 14. Wang Y, Xu H, Mizoguchi K, et al. Intestinal ischemia induces late preconditioning against myocardial infarction: a role for inducible nitric oxide synthase. Cardiovasc Res, 2001,49 (2):391-398.
- 15. Kuntscher MV, Kastell T, Altmann J, et al. Acute remote ischemic preconditioning II: the role of nitric oxide. Microsurgery, 2002,22 (6):227-231.
- 16. Xu C, Lu Y, Pan Z, et al. The muscle-specific microRNAs miR-1 and miR-133 produce opposing effects on apoptosis by targeting HSP60, HSP70 and caspase-9 in cardiomyocytes. J Cell Sci, 2007,120 (Pt 17):3045-3052.
- 17. Kwon C, Han Z, Olson EN, et al. MicroRNA1 influences cardiac differentiation in Drosophila and regulates Notch signaling. Proc Natl Acad Sci U S A, 2005,102 (52):18986-18991.
- 18. Chen JF, Mandel EM, Thomson JM, et al. The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat Genet, 2006,38 (2):228-233.
- 19. Heusch G, Boengler K, Schulz R. Cardioprotection: nitric oxide, protein kinases, and mitochondria. Circulation, 2008,118 (19):1915-1919.
- 20. Latchman DS. Heat shock proteins and cardiac protection.
- 21. Hampton CR, Shimamoto A, Rothnie CL, et al. HSP70.1 and -70.3 are required for late-phase protection induced by ischemic preconditioning of mouse hearts. Am J Physiol Heart Circ Physiol, 2003,285 (2):H866-874.
- 22. Wang G, Liem DA, Vondriska TM, et al. Nitric oxide donors protect murine myocardium against infarction via modulation of mitochondrial permeability transition. Am J Physiol Heart Circ Physiol, 2005,288 (3):H1290-1295.
- 23. Precht TA, Phelps RA, Linseman DA, et al. The permeability transition pore triggers Bax translocation to mitochondria during neuronal apoptosis. Cell Death Differ, 2005,12 (3):255-265.
- 24. Schmitt JP, Schroder J, Schunkert H, et al. Role of apoptosis in myocardial stunning after open heart surgery. Ann Thorac Surg, 2002,73 (4):1229-1235.
- 25. Penna C, Tullio F, Merlino A, et al. Postconditioning cardioprotection against infarct size and post-ischemic systolic dysfunction is influenced by gender. Basic Res Cardiol, 2009,104 (4):390-402.