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RBM3 and CIRP expressions in targeted temperature management treated cardiac arrest patients—A prospective single center study


Autoři: Lisa-Maria Rosenthal aff001;  Christoph Leithner aff003;  Giang Tong aff001;  Kaspar Josche Streitberger aff002;  Jana Krech aff001;  Christian Storm aff004;  Katharina Rose Luise Schmitt aff001
Působiště autorů: Dept. for Congenital Heart Disease/Pediatric Cardiology, Deutsches Herzzentrum Berlin, Berlin, Germany aff001;  Berlin Institute of Health, Berlin, Germany aff002;  Dept. of Neurology, Charité Universtitätsmedizin Berlin, Berlin, Germany aff003;  Dept. of Internal Medicine, Nephrology and Intensive Care, Charité Universitätsmedizin Berlin, Berlin, Germany aff004;  Dept. for Pediatric Cardiology, Charité Universitätsmedizin Berlin, Berlin, Germany aff005;  DHZK (German Centre for Cardiovascular Research), Berlin, Germany aff006
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0226005

Souhrn

Background

Management of cardiac arrest patients includes active body temperature control and strict prevention of fever to avoid further neurological damage. Cold-shock proteins RNA-binding motif 3 (RBM3) and cold inducible RNA-binding protein (CIRP) expressions are induced in vitro in response to hypothermia and play a key role in hypothermia-induced neuroprotection.

Objective

To measure gene expressions of RBM3, CIRP, and inflammatory biomarkers in whole blood samples from targeted temperature management (TTM)-treated post-cardiac arrest patients for the potential application as clinical biomarkers for the efficacy of TTM treatment.

Methods

A prospective single center trial with the inclusion of 22 cardiac arrest patients who were treated with TTM (33°C for 24 hours) after ROSC was performed. RBM3, CIRP, interleukin 6 (IL-6), monocyte chemotactic protein 1 (MCP-1), and inducible nitric oxide synthase (iNOS) mRNA expressions were quantified by RT-qPCR. Serum RBM3 protein concentration was quantified using an enzyme-linked immunosorbent assay (ELISA).

Results

RBM3 mRNA expression was significantly induced in post-cardiac arrest patients in response to TTM. RBM3 mRNA was increased 2.2-fold compared to before TTM. A similar expression kinetic of 1.4-fold increase was observed for CIRP mRNA, but did not reached significancy. Serum RBM3 protein was not increased in response to TTM. IL-6 and MCP-1 expression peaked after ROSC and then significantly decreased. iNOS expression was significantly increased 24h after return of spontaneous circulation (ROSC) and TTM.

Conclusions

RBM3 is temperature regulated in patients treated with TTM after CA and ROSC. RBM3 is a possible biomarker candidate to ensure the efficacy of TTM treatment in post-cardiac arrest patients and its pharmacological induction could be a potential future intervention strategy that warrants further research.

Klíčová slova:

Gene expression – Inflammation – Enzyme-linked immunoassays – Protein expression – Serum proteins – Body temperature – Cardiac arrest – Neuronal death


Zdroje

1. Efendijev I, Folger D, Raj R, Reinikainen M, Pekkarinen PT, Litonius E, et al. Outcomes and healthcare-associated costs one year after intensive care-treated cardiac arrest. Resuscitation. 2018. Epub 2018/07/01. doi: 10.1016/j.resuscitation.2018.06.028 29958958.

2. Lemiale V, Dumas F, Mongardon N, Giovanetti O, Charpentier J, Chiche JD, et al. Intensive care unit mortality after cardiac arrest: the relative contribution of shock and brain injury in a large cohort. Intensive care medicine. 2013;39(11):1972–80. Epub 2013/08/15. doi: 10.1007/s00134-013-3043-4 23942856.

3. Schmitt KR, Tong G, Berger F. Mechanisms of hypothermia-induced cell protection in the brain. Molecular and cellular pediatrics. 2014;1(1):7. Epub 2015/11/15. doi: 10.1186/s40348-014-0007-x 26567101.

4. Yenari MA, Han HS. Neuroprotective mechanisms of hypothermia in brain ischaemia. Nature reviews Neuroscience. 2012;13(4):267–78. Epub 2012/02/23. doi: 10.1038/nrn3174 22353781.

5. Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. The New England journal of medicine. 2002;346(8):557–63. Epub 2002/02/22. doi: 10.1056/NEJMoa003289 11856794.

6. Mild Therapeutic Hypothermia to Improve the Neurologic Outcome after Cardiac Arrest. New England Journal of Medicine. 2002;346(8):549–56. doi: 10.1056/NEJMoa012689 11856793.

7. Nielsen N, Wetterslev J, Cronberg T, Erlinge D, Gasche Y, Hassager C, et al. Targeted temperature management at 33 degrees C versus 36 degrees C after cardiac arrest. The New England journal of medicine. 2013;369(23):2197–206. Epub 2013/11/19. doi: 10.1056/NEJMoa1310519 24237006.

8. Danno S, Nishiyama H, Higashitsuji H, Yokoi H, Xue JH, Itoh K, et al. Increased transcript level of RBM3, a member of the glycine-rich RNA-binding protein family, in human cells in response to cold stress. Biochemical and biophysical research communications. 1997;236(3):804–7. Epub 1997/07/30. doi: 10.1006/bbrc.1997.7059 9245737.

9. Nishiyama H, Itoh K, Kaneko Y, Kishishita M, Yoshida O, Fujita J. A glycine-rich RNA-binding protein mediating cold-inducible suppression of mammalian cell growth. The Journal of cell biology. 1997;137(4):899–908. Epub 1997/05/19. doi: 10.1083/jcb.137.4.899 9151692.

10. Jackson TC, Manole MD, Kotermanski SE, Jackson EK, Clark RS, Kochanek PM. Cold stress protein RBM3 responds to temperature change in an ultra-sensitive manner in young neurons. Neuroscience. 2015;305:268–78. Epub 2015/08/13. doi: 10.1016/j.neuroscience.2015.08.012 26265550.

11. Tong G, Endersfelder S, Rosenthal LM, Wollersheim S, Sauer IM, Buhrer C, et al. Effects of moderate and deep hypothermia on RNA-binding proteins RBM3 and CIRP expressions in murine hippocampal brain slices. Brain research. 2013;1504:74–84. Epub 2013/02/19. doi: 10.1016/j.brainres.2013.01.041 23415676.

12. Wellmann S, Buhrer C, Moderegger E, Zelmer A, Kirschner R, Koehne P, et al. Oxygen-regulated expression of the RNA-binding proteins RBM3 and CIRP by a HIF-1-independent mechanism. Journal of cell science. 2004;117(Pt 9):1785–94. Epub 2004/04/13. doi: 10.1242/jcs.01026 15075239.

13. Rosenthal LM, Tong G, Walker C, Wowro SJ, Krech J, Pfitzer C, et al. Neuroprotection via RNA-binding protein RBM3 expression is regulated by hypothermia but not by hypoxia in human SK-N-SH neurons. Hypoxia (Auckland, NZ). 2017;5:33–43. Epub 2017/06/06. doi: 10.2147/hp.S132462 28580361.

14. Lebsack TW, Fa V, Woods CC, Gruener R, Manziello AM, Pecaut MJ, et al. Microarray analysis of spaceflown murine thymus tissue reveals changes in gene expression regulating stress and glucocorticoid receptors. Journal of cellular biochemistry. 2010;110(2):372–81. Epub 2010/03/10. doi: 10.1002/jcb.22547 20213684.

15. Zhu X, Buhrer C, Wellmann S. Cold-inducible proteins CIRP and RBM3, a unique couple with activities far beyond the cold. Cellular and molecular life sciences: CMLS. 2016;73(20):3839–59. Epub 2016/05/06. doi: 10.1007/s00018-016-2253-7 27147467.

16. Wellmann S, Truss M, Bruder E, Tornillo L, Zelmer A, Seeger K, et al. The RNA-binding protein RBM3 is required for cell proliferation and protects against serum deprivation-induced cell death. Pediatric research. 2010;67(1):35–41. Epub 2009/09/23. doi: 10.1203/PDR.0b013e3181c13326 19770690.

17. Saito K, Fukuda N, Matsumoto T, Iribe Y, Tsunemi A, Kazama T, et al. Moderate low temperature preserves the stemness of neural stem cells and suppresses apoptosis of the cells via activation of the cold-inducible RNA binding protein. Brain research. 2010;1358:20–9. Epub 2010/08/26. doi: 10.1016/j.brainres.2010.08.048 20735994.

18. Li S, Zhang Z, Xue J, Liu A, Zhang H. Cold-inducible RNA binding protein inhibits H(2)O(2)-induced apoptosis in rat cortical neurons. Brain research. 2012;1441:47–52. Epub 2012/02/03. doi: 10.1016/j.brainres.2011.12.053 22297174.

19. Chip S, Zelmer A, Ogunshola OO, Felderhoff-Mueser U, Nitsch C, Buhrer C, et al. The RNA-binding protein RBM3 is involved in hypothermia induced neuroprotection. Neurobiology of disease. 2011;43(2):388–96. Epub 2011/04/30. doi: 10.1016/j.nbd.2011.04.010 21527344.

20. Peretti D, Bastide A, Radford H, Verity N, Molloy C, Martin MG, et al. RBM3 mediates structural plasticity and protective effects of cooling in neurodegeneration. Nature. 2015;518(7538):236–9. Epub 2015/01/22. doi: 10.1038/nature14142 25607368.

21. Zhou M, Yang WL, Ji Y, Qiang X, Wang P. Cold-inducible RNA-binding protein mediates neuroinflammation in cerebral ischemia. Biochimica et biophysica acta. 2014;1840(7):2253–61. Epub 2014/03/13. doi: 10.1016/j.bbagen.2014.02.027 24613680.

22. Xue JH, Nonoguchi K, Fukumoto M, Sato T, Nishiyama H, Higashitsuji H, et al. Effects of ischemia and H2O2 on the cold stress protein CIRP expression in rat neuronal cells. Free radical biology & medicine. 1999;27(11–12):1238–44. Epub 2000/01/21. doi: 10.1016/s0891-5849(99)00158-6 10641716.

23. Liu J, Xue J, Zhang H, Li S, Liu Y, Xu D, et al. Cloning, expression, and purification of cold inducible RNA-binding protein and its neuroprotective mechanism of action. Brain research. 2015;1597:189–95. Epub 2014/12/17. doi: 10.1016/j.brainres.2014.11.061 25498861.

24. Qiang X, Yang WL, Wu R, Zhou M, Jacob A, Dong W, et al. Cold-inducible RNA-binding protein (CIRP) triggers inflammatory responses in hemorrhagic shock and sepsis. Nature medicine. 2013;19(11):1489–95. Epub 2013/10/08. doi: 10.1038/nm.3368 24097189.

25. Zhou Y, Dong H, Zhong Y, Huang J, Lv J, Li J. The Cold-Inducible RNA-Binding Protein (CIRP) Level in Peripheral Blood Predicts Sepsis Outcome. PloS one. 2015;10(9):e0137721. Epub 2015/09/12. doi: 10.1371/journal.pone.0137721 26361390.

26. Nolan JP, Soar J, Cariou A, Cronberg T, Moulaert VR, Deakin CD, et al. European Resuscitation Council and European Society of Intensive Care Medicine Guidelines for Post-resuscitation Care 2015: Section 5 of the European Resuscitation Council Guidelines for Resuscitation 2015. Resuscitation. 2015;95:202–22. Epub 2015/10/20. doi: 10.1016/j.resuscitation.2015.07.018 26477702.

27. Streitberger KJ, Leithner C, Wattenberg M, Tonner PH, Hasslacher J, Joannidis M, et al. Neuron-Specific Enolase Predicts Poor Outcome After Cardiac Arrest and Targeted Temperature Management: A Multicenter Study on 1,053 Patients. Critical care medicine. 2017;45(7):1145–51. Epub 2017/04/21. doi: 10.1097/CCM.0000000000002335 28426467.

28. Pilotte J, Cunningham BA, Edelman GM, Vanderklish PW. Developmentally regulated expression of the cold-inducible RNA-binding motif protein 3 in euthermic rat brain. Brain research. 2009;1258:12–24. Epub 2009/01/20. doi: 10.1016/j.brainres.2008.12.050 19150436.

29. Cui Z, Zhang J, Bao G, Xu G, Sun Y, Wang L, et al. Spatiotemporal profile and essential role of RBM3 expression after spinal cord injury in adult rats. Journal of molecular neuroscience: MN. 2014;54(2):252–63. Epub 2014/03/29. doi: 10.1007/s12031-014-0282-y 24668366.

30. Zhu X, Zelmer A, Kapfhammer JP, Wellmann S. Cold-inducible RBM3 inhibits PERK phosphorylation through cooperation with NF90 to protect cells from endoplasmic reticulum stress. FASEB journal: official publication of the Federation of American Societies for Experimental Biology. 2016;30(2):624–34. Epub 2015/10/17. doi: 10.1096/fj.15-274639 26472337.

31. Nolan JP, Neumar RW, Adrie C, Aibiki M, Berg RA, Bottiger BW, et al. Post-cardiac arrest syndrome: epidemiology, pathophysiology, treatment, and prognostication. A Scientific Statement from the International Liaison Committee on Resuscitation; the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; the Council on Stroke. Resuscitation. 2008;79(3):350–79. Epub 2008/10/31. doi: 10.1016/j.resuscitation.2008.09.017 18963350.

32. Bro-Jeppesen J, Johansson PI, Kjaergaard J, Wanscher M, Ostrowski SR, Bjerre M, et al. Level of systemic inflammation and endothelial injury is associated with cardiovascular dysfunction and vasopressor support in post-cardiac arrest patients. Resuscitation. 2017;121:179–86. Epub 2017/09/28. doi: 10.1016/j.resuscitation.2017.09.019 28947390.

33. Shi J, Dai W, Kloner RA. Therapeutic Hypothermia Reduces the Inflammatory Response Following Ischemia/Reperfusion Injury in Rat Hearts. Therapeutic hypothermia and temperature management. 2017;7(3):162–70. Epub 2017/03/25. doi: 10.1089/ther.2016.0042 28338422.

34. Matsumoto H, Ogura H, Shimizu K, Ikeda M, Hirose T, Matsuura H, et al. The clinical importance of a cytokine network in the acute phase of sepsis. Scientific reports. 2018;8(1):13995. Epub 2018/09/20. doi: 10.1038/s41598-018-32275-8 30228372.

35. Kern KB, Berg RA, Hilwig RW, Larson DF, Gaballa MA. Myocardial cytokine IL-8 and nitric oxide synthase activity during and after resuscitation: preliminary observations in regards to post-resuscitation myocardial dysfunction. Resuscitation. 2008;77(3):401–9. Epub 2008/03/25. doi: 10.1016/j.resuscitation.2008.01.026 18359140.

36. Adams JA, Wu D, Bassuk J, Arias J, Lozano H, Kurlansky P, et al. Nitric oxide synthase isoform inhibition before whole body ischemia reperfusion in pigs: vital or protective? Resuscitation. 2007;74(3):516–25. Epub 2007/05/01. doi: 10.1016/j.resuscitation.2007.02.009 17466432.


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