Skip to main content
Erschienen in: Basic Research in Cardiology 1/2020

01.01.2020 | Original Contribution

Egr-1 functions as a master switch regulator of remote ischemic preconditioning-induced cardioprotection

verfasst von: M. Billah, A. Ridiandries, B. S. Rayner, U. K. Allahwala, A. Dona, L. M. Khachigian, R. Bhindi

Erschienen in: Basic Research in Cardiology | Ausgabe 1/2020

Einloggen, um Zugang zu erhalten

Abstract

Despite improved treatment options myocardial infarction (MI) is still a leading cause of mortality and morbidity worldwide. Remote ischemic preconditioning (RIPC) is a mechanistic process that reduces myocardial infarction size and protects against ischemia reperfusion (I/R) injury. The zinc finger transcription factor early growth response-1 (Egr-1) is integral to the biological response to I/R, as its upregulation mediates the increased expression of inflammatory and prothrombotic processes. We aimed to determine the association and/or role of Egr-1 expression with the molecular mechanisms controlling the cardioprotective effects of RIPC. This study used H9C2 cells in vitro and a rat model of cardiac ischemia reperfusion (I/R) injury. We silenced Egr-1 with DNAzyme (ED5) in vitro and in vivo, before three cycles of RIPC consisting of alternating 5 min hypoxia and normoxia in cells or hind-limb ligation and release in the rat, followed by hypoxic challenge in vitro and I/R injury in vivo. Post-procedure, ED5 administration led to a significant increase in infarct size compared to controls (65.90 ± 2.38% vs. 41.00 ± 2.83%, p < 0.0001) following administration prior to RIPC in vivo, concurrent with decreased plasma IL-6 levels (118.30 ± 4.30 pg/ml vs. 130.50 ± 1.29 pg/ml, p < 0.05), downregulation of the cardioprotective JAK–STAT pathway, and elevated myocardial endothelial dysfunction. In vitro, ED5 administration abrogated IL-6 mRNA expression in H9C2 cells subjected to RIPC (0.95 ± 0.20 vs. 6.08 ± 1.40-fold relative to the control group, p < 0.05), resulting in increase in apoptosis (4.76 ± 0.70% vs. 2.23 ± 0.34%, p < 0.05) and loss of mitochondrial membrane potential (0.57 ± 0.11% vs. 1.0 ± 0.14%-fold relative to control, p < 0.05) in recipient cells receiving preconditioned media from the DNAzyme treated donor cells. This study suggests that Egr-1 functions as a master regulator of remote preconditioning inducing a protective effect against myocardial I/R injury through IL-6-dependent JAK–STAT signaling.
Literatur
3.
Zurück zum Zitat Aebert H, Cornelius T, Ehr T, Holmer SR, Birnbaum DE, Riegger GA, Schunkert H (1997) Expression of immediate early genes after cardioplegic arrest and reperfusion. Ann Thorac Surg 63:1669–1675CrossRef Aebert H, Cornelius T, Ehr T, Holmer SR, Birnbaum DE, Riegger GA, Schunkert H (1997) Expression of immediate early genes after cardioplegic arrest and reperfusion. Ann Thorac Surg 63:1669–1675CrossRef
13.
Zurück zum Zitat Botker HE, Hausenloy D, Andreadou I, Antonucci S, Boengler K, Davidson SM, Deshwal S, Devaux Y, Di Lisa F, Di Sante M, Efentakis P, Femmino S, Garcia-Dorado D, Giricz Z, Ibanez B, Iliodromitis E, Kaludercic N, Kleinbongard P, Neuhauser M, Ovize M, Pagliaro P, Rahbek-Schmidt M, Ruiz-Meana M, Schluter KD, Schulz R, Skyschally A, Wilder C, Yellon DM, Ferdinandy P, Heusch G (2018) Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection. Basic Res Cardiol 113:39. https://doi.org/10.1007/s00395-018-0696-8 CrossRefPubMedPubMedCentral Botker HE, Hausenloy D, Andreadou I, Antonucci S, Boengler K, Davidson SM, Deshwal S, Devaux Y, Di Lisa F, Di Sante M, Efentakis P, Femmino S, Garcia-Dorado D, Giricz Z, Ibanez B, Iliodromitis E, Kaludercic N, Kleinbongard P, Neuhauser M, Ovize M, Pagliaro P, Rahbek-Schmidt M, Ruiz-Meana M, Schluter KD, Schulz R, Skyschally A, Wilder C, Yellon DM, Ferdinandy P, Heusch G (2018) Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection. Basic Res Cardiol 113:39. https://​doi.​org/​10.​1007/​s00395-018-0696-8 CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Botker HE, Kharbanda R, Schmidt MR, Bottcher M, Kaltoft AK, Terkelsen CJ, Munk K, Andersen NH, Hansen TM, Trautner S, Lassen JF, Christiansen EH, Krusell LR, Kristensen SD, Thuesen L, Nielsen SS, Rehling M, Sorensen HT, Redington AN, Nielsen TT (2010) Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial. Lancet 375:727–734. https://doi.org/10.1016/S0140-6736(09)62001-8 CrossRefPubMed Botker HE, Kharbanda R, Schmidt MR, Bottcher M, Kaltoft AK, Terkelsen CJ, Munk K, Andersen NH, Hansen TM, Trautner S, Lassen JF, Christiansen EH, Krusell LR, Kristensen SD, Thuesen L, Nielsen SS, Rehling M, Sorensen HT, Redington AN, Nielsen TT (2010) Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial. Lancet 375:727–734. https://​doi.​org/​10.​1016/​S0140-6736(09)62001-8 CrossRefPubMed
15.
Zurück zum Zitat Brand T, Sharma HS, Fleischmann KE, Duncker DJ, McFalls EO, Verdouw PD, Schaper W (1992) Proto-oncogene expression in porcine myocardium subjected to ischemia and reperfusion. Circ Res 71:1351–1360CrossRef Brand T, Sharma HS, Fleischmann KE, Duncker DJ, McFalls EO, Verdouw PD, Schaper W (1992) Proto-oncogene expression in porcine myocardium subjected to ischemia and reperfusion. Circ Res 71:1351–1360CrossRef
19.
Zurück zum Zitat Cheung MM, Kharbanda RK, Konstantinov IE, Shimizu M, Frndova H, Li J, Holtby HM, Cox PN, Smallhorn JF, Van Arsdell GS, Redington AN (2006) Randomized controlled trial of the effects of remote ischemic preconditioning on children undergoing cardiac surgery: first clinical application in humans. J Am Coll Cardiol 47:2277–2282. https://doi.org/10.1016/j.jacc.2006.01.066 CrossRefPubMed Cheung MM, Kharbanda RK, Konstantinov IE, Shimizu M, Frndova H, Li J, Holtby HM, Cox PN, Smallhorn JF, Van Arsdell GS, Redington AN (2006) Randomized controlled trial of the effects of remote ischemic preconditioning on children undergoing cardiac surgery: first clinical application in humans. J Am Coll Cardiol 47:2277–2282. https://​doi.​org/​10.​1016/​j.​jacc.​2006.​01.​066 CrossRefPubMed
20.
Zurück zum Zitat Chouchani ET, Methner C, Nadtochiy SM, Logan A, Pell VR, Ding S, James AM, Cocheme HM, Reinhold J, Lilley KS, Partridge L, Fearnley IM, Robinson AJ, Hartley RC, Smith RA, Krieg T, Brookes PS, Murphy MP (2013) Cardioprotection by S-nitrosation of a cysteine switch on mitochondrial complex I. Nat Med 19:753–759. https://doi.org/10.1038/nm.3212 CrossRefPubMedPubMedCentral Chouchani ET, Methner C, Nadtochiy SM, Logan A, Pell VR, Ding S, James AM, Cocheme HM, Reinhold J, Lilley KS, Partridge L, Fearnley IM, Robinson AJ, Hartley RC, Smith RA, Krieg T, Brookes PS, Murphy MP (2013) Cardioprotection by S-nitrosation of a cysteine switch on mitochondrial complex I. Nat Med 19:753–759. https://​doi.​org/​10.​1038/​nm.​3212 CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Cocheme HM, Logan A, Prime TA, Abakumova I, Quin C, McQuaker SJ, Patel JV, Fearnley IM, James AM, Porteous CM, Smith RA, Hartley RC, Partridge L, Murphy MP (2012) Using the mitochondria-targeted ratiometric mass spectrometry probe MitoB to measure H2O2 in living Drosophila. Nat Protoc 7:946–958. https://doi.org/10.1038/nprot.2012.035 CrossRefPubMed Cocheme HM, Logan A, Prime TA, Abakumova I, Quin C, McQuaker SJ, Patel JV, Fearnley IM, James AM, Porteous CM, Smith RA, Hartley RC, Partridge L, Murphy MP (2012) Using the mitochondria-targeted ratiometric mass spectrometry probe MitoB to measure H2O2 in living Drosophila. Nat Protoc 7:946–958. https://​doi.​org/​10.​1038/​nprot.​2012.​035 CrossRefPubMed
22.
Zurück zum Zitat Crompton M (1999) The mitochondrial permeability transition pore and its role in cell death. Biochem J 341(Pt 2):233–249CrossRefPubMedCentral Crompton M (1999) The mitochondrial permeability transition pore and its role in cell death. Biochem J 341(Pt 2):233–249CrossRefPubMedCentral
25.
Zurück zum Zitat Davidson SM, Arjun S, Basalay MV, Bell RM, Bromage DI, Botker HE, Carr RD, Cunningham J, Ghosh AK, Heusch G, Ibanez B, Kleinbongard P, Lecour S, Maddock H, Ovize M, Walker M, Wiart M, Yellon DM (2018) The 10th Biennial Hatter Cardiovascular Institute workshop: cellular protection-evaluating new directions in the setting of myocardial infarction, ischaemic stroke, and cardio-oncology. Basic Res Cardiol 113:43. https://doi.org/10.1007/s00395-018-0704-z CrossRefPubMedPubMedCentral Davidson SM, Arjun S, Basalay MV, Bell RM, Bromage DI, Botker HE, Carr RD, Cunningham J, Ghosh AK, Heusch G, Ibanez B, Kleinbongard P, Lecour S, Maddock H, Ovize M, Walker M, Wiart M, Yellon DM (2018) The 10th Biennial Hatter Cardiovascular Institute workshop: cellular protection-evaluating new directions in the setting of myocardial infarction, ischaemic stroke, and cardio-oncology. Basic Res Cardiol 113:43. https://​doi.​org/​10.​1007/​s00395-018-0704-z CrossRefPubMedPubMedCentral
28.
Zurück zum Zitat Dickson EW, Porcaro WA, Fenton RA, Heard SO, Reindhardt CP, Renzi FP, Przyklenk K (2000) “Preconditioning at a distance” in the isolated rabbit heart. Acad Emerg Med 7:311–317CrossRef Dickson EW, Porcaro WA, Fenton RA, Heard SO, Reindhardt CP, Renzi FP, Przyklenk K (2000) “Preconditioning at a distance” in the isolated rabbit heart. Acad Emerg Med 7:311–317CrossRef
29.
Zurück zum Zitat Dickson EW, Reinhardt CP, Renzi FP, Becker RC, Porcaro WA, Heard SO (1999) Ischemic preconditioning may be transferable via whole blood transfusion: preliminary evidence. J Thromb Thrombolysis 8:123–129CrossRef Dickson EW, Reinhardt CP, Renzi FP, Becker RC, Porcaro WA, Heard SO (1999) Ischemic preconditioning may be transferable via whole blood transfusion: preliminary evidence. J Thromb Thrombolysis 8:123–129CrossRef
30.
31.
Zurück zum Zitat Gashler A, Sukhatme VP (1995) Early growth response protein 1 (Egr-1): prototype of a zinc-finger family of transcription factors. Prog Mol Biol Transl Sci 50:191–224 Gashler A, Sukhatme VP (1995) Early growth response protein 1 (Egr-1): prototype of a zinc-finger family of transcription factors. Prog Mol Biol Transl Sci 50:191–224
32.
39.
Zurück zum Zitat Hausenloy DJ, Kharbanda RK, Moller UK, Ramlall M, Aaroe J, Butler R, Bulluck H, Clayton T, Dana A, Dodd M, Engstrom T, Evans R, Lassen JF, Christensen EF, Garcia-Ruiz JM, Gorog DA, Hjort J, Houghton RF, Ibanez B, Knight R, Lippert FK, Lonborg JT, Maeng M, Milasinovic D, More R, Nicholas JM, Jensen LO, Perkins A, Radovanovic N, Rakhit RD, Ravkilde J, Ryding AD, Schmidt MR, Riddervold IS, Sorensen HT, Stankovic G, Varma M, Webb I, Terkelsen CJ, Greenwood JP, Yellon DM, Botker HE, Investigators C-E-P (2019) Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial. Lancet 394:1415–1424. https://doi.org/10.1016/S0140-6736(19)32039-2 CrossRefPubMedPubMedCentral Hausenloy DJ, Kharbanda RK, Moller UK, Ramlall M, Aaroe J, Butler R, Bulluck H, Clayton T, Dana A, Dodd M, Engstrom T, Evans R, Lassen JF, Christensen EF, Garcia-Ruiz JM, Gorog DA, Hjort J, Houghton RF, Ibanez B, Knight R, Lippert FK, Lonborg JT, Maeng M, Milasinovic D, More R, Nicholas JM, Jensen LO, Perkins A, Radovanovic N, Rakhit RD, Ravkilde J, Ryding AD, Schmidt MR, Riddervold IS, Sorensen HT, Stankovic G, Varma M, Webb I, Terkelsen CJ, Greenwood JP, Yellon DM, Botker HE, Investigators C-E-P (2019) Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial. Lancet 394:1415–1424. https://​doi.​org/​10.​1016/​S0140-6736(19)32039-2 CrossRefPubMedPubMedCentral
40.
Zurück zum Zitat Hausenloy DJ, Mwamure PK, Venugopal V, Harris J, Barnard M, Grundy E, Ashley E, Vichare S, Di Salvo C, Kolvekar S, Hayward M, Keogh B, MacAllister RJ, Yellon DM (2007) Effect of remote ischaemic preconditioning on myocardial injury in patients undergoing coronary artery bypass graft surgery: a randomised controlled trial. Lancet 370:575–579. https://doi.org/10.1016/S0140-6736(07)61296-3 CrossRefPubMed Hausenloy DJ, Mwamure PK, Venugopal V, Harris J, Barnard M, Grundy E, Ashley E, Vichare S, Di Salvo C, Kolvekar S, Hayward M, Keogh B, MacAllister RJ, Yellon DM (2007) Effect of remote ischaemic preconditioning on myocardial injury in patients undergoing coronary artery bypass graft surgery: a randomised controlled trial. Lancet 370:575–579. https://​doi.​org/​10.​1016/​S0140-6736(07)61296-3 CrossRefPubMed
52.
Zurück zum Zitat Ikeda U, Ohkawa F, Seino Y, Yamamoto K, Hidaka Y, Kasahara T, Kawai T, Shimada K (1992) Serum interleukin 6 levels become elevated in acute myocardial infarction. J Mol Cell Cardiol 24:579–584CrossRef Ikeda U, Ohkawa F, Seino Y, Yamamoto K, Hidaka Y, Kasahara T, Kawai T, Shimada K (1992) Serum interleukin 6 levels become elevated in acute myocardial infarction. J Mol Cell Cardiol 24:579–584CrossRef
55.
Zurück zum Zitat Kimes BW, Brandt BL (1976) Properties of a clonal muscle cell line from rat heart. Exp Cell Res 98:367–381CrossRef Kimes BW, Brandt BL (1976) Properties of a clonal muscle cell line from rat heart. Exp Cell Res 98:367–381CrossRef
69.
Zurück zum Zitat Liauw SK, Rubin BB, Lindsay TF, Romaschin AD, Walker PM (1996) Sequential ischemia/reperfusion results in contralateral skeletal muscle salvage. Am J Physiol 270:H1407–H1413PubMed Liauw SK, Rubin BB, Lindsay TF, Romaschin AD, Walker PM (1996) Sequential ischemia/reperfusion results in contralateral skeletal muscle salvage. Am J Physiol 270:H1407–H1413PubMed
70.
Zurück zum Zitat Lindsey ML, Bolli R, Canty JM Jr, Du XJ, Frangogiannis NG, Frantz S, Gourdie RG, Holmes JW, Jones SP, Kloner RA, Lefer DJ, Liao R, Murphy E, Ping P, Przyklenk K, Recchia FA, Schwartz Longacre L, Ripplinger CM, Van Eyk JE, Heusch G (2018) Guidelines for experimental models of myocardial ischemia and infarction. Am J Physiol Heart Circ Physiol 314:H812–H838. https://doi.org/10.1152/ajpheart.00335.2017 CrossRefPubMedPubMedCentral Lindsey ML, Bolli R, Canty JM Jr, Du XJ, Frangogiannis NG, Frantz S, Gourdie RG, Holmes JW, Jones SP, Kloner RA, Lefer DJ, Liao R, Murphy E, Ping P, Przyklenk K, Recchia FA, Schwartz Longacre L, Ripplinger CM, Van Eyk JE, Heusch G (2018) Guidelines for experimental models of myocardial ischemia and infarction. Am J Physiol Heart Circ Physiol 314:H812–H838. https://​doi.​org/​10.​1152/​ajpheart.​00335.​2017 CrossRefPubMedPubMedCentral
75.
Zurück zum Zitat Marubayashi S, Oshiro Y, Maeda T, Fukuma K, Okada K, Hinoi T, Ikeda M, Yamada K, Itoh H, Dohi K (1997) Protective effect of monoclonal antibodies to adhesion molecules on rat liver ischemia-reperfusion injury. Surgery 122:45–52CrossRef Marubayashi S, Oshiro Y, Maeda T, Fukuma K, Okada K, Hinoi T, Ikeda M, Yamada K, Itoh H, Dohi K (1997) Protective effect of monoclonal antibodies to adhesion molecules on rat liver ischemia-reperfusion injury. Surgery 122:45–52CrossRef
79.
Zurück zum Zitat Miyao Y, Yasue H, Ogawa H, Misumi I, Masuda T, Sakamoto T, Morita E (1993) Elevated plasma interleukin-6 levels in patients with acute myocardial infarction. Am Heart J 126:1299–1304CrossRef Miyao Y, Yasue H, Ogawa H, Misumi I, Masuda T, Sakamoto T, Morita E (1993) Elevated plasma interleukin-6 levels in patients with acute myocardial infarction. Am Heart J 126:1299–1304CrossRef
83.
Zurück zum Zitat Nakano H, Kuzume M, Namatame K, Yamaguchi M, Kumada K (1995) Efficacy of intraportal injection of anti-ICAM-1 monoclonal antibody against liver cell injury following warm ischemia in the rat. Am J Surg 170:64–66CrossRef Nakano H, Kuzume M, Namatame K, Yamaguchi M, Kumada K (1995) Efficacy of intraportal injection of anti-ICAM-1 monoclonal antibody against liver cell injury following warm ischemia in the rat. Am J Surg 170:64–66CrossRef
84.
Zurück zum Zitat Nguyen HQ, Hoffman-Liebermann B, Liebermann DA (1993) The zinc finger transcription factor Egr-1 is essential for and restricts differentiation along the macrophage lineage. Cell 72:197–209CrossRef Nguyen HQ, Hoffman-Liebermann B, Liebermann DA (1993) The zinc finger transcription factor Egr-1 is essential for and restricts differentiation along the macrophage lineage. Cell 72:197–209CrossRef
89.
Zurück zum Zitat Peters M, Jacobs S, Ehlers M, Vollmer P, Mullberg J, Wolf E, Brem G, Meyer zum Buschenfelde KH, Rose-John S (1996) The function of the soluble interleukin 6 (IL-6) receptor in vivo: sensitization of human soluble IL-6 receptor transgenic mice towards IL-6 and prolongation of the plasma half-life of IL-6. J Exp Med 183:1399–1406CrossRef Peters M, Jacobs S, Ehlers M, Vollmer P, Mullberg J, Wolf E, Brem G, Meyer zum Buschenfelde KH, Rose-John S (1996) The function of the soluble interleukin 6 (IL-6) receptor in vivo: sensitization of human soluble IL-6 receptor transgenic mice towards IL-6 and prolongation of the plasma half-life of IL-6. J Exp Med 183:1399–1406CrossRef
93.
Zurück zum Zitat Rayner BS, Figtree GA, Sabaretnam T, Shang P, Mazhar J, Weaver JC, Lay WN, Witting PK, Hunyor SN, Grieve SM, Khachigian LM, Bhindi R (2013) Selective inhibition of the master regulator transcription factor Egr-1 with catalytic oligonucleotides reduces myocardial injury and improves left ventricular systolic function in a preclinical model of myocardial infarction. J Am Heart Assoc 2:e000023. https://doi.org/10.1161/JAHA.113.000023 CrossRefPubMedPubMedCentral Rayner BS, Figtree GA, Sabaretnam T, Shang P, Mazhar J, Weaver JC, Lay WN, Witting PK, Hunyor SN, Grieve SM, Khachigian LM, Bhindi R (2013) Selective inhibition of the master regulator transcription factor Egr-1 with catalytic oligonucleotides reduces myocardial injury and improves left ventricular systolic function in a preclinical model of myocardial infarction. J Am Heart Assoc 2:e000023. https://​doi.​org/​10.​1161/​JAHA.​113.​000023 CrossRefPubMedPubMedCentral
96.
Zurück zum Zitat Romano M, Sironi M, Toniatti C, Polentarutti N, Fruscella P, Ghezzi P, Faggioni R, Luini W, van Hinsbergh V, Sozzani S, Bussolino F, Poli V, Ciliberto G, Mantovani A (1997) Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment. Immunity 6:315–325CrossRef Romano M, Sironi M, Toniatti C, Polentarutti N, Fruscella P, Ghezzi P, Faggioni R, Luini W, van Hinsbergh V, Sozzani S, Bussolino F, Poli V, Ciliberto G, Mantovani A (1997) Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment. Immunity 6:315–325CrossRef
98.
Zurück zum Zitat Saini HK, Xu YJ, Zhang M, Liu PP, Kirshenbaum LA, Dhalla NS (2005) Role of tumour necrosis factor-alpha and other cytokines in ischemia-reperfusion-induced injury in the heart. Exp Clin Cardiol 10:213–222PubMedPubMedCentral Saini HK, Xu YJ, Zhang M, Liu PP, Kirshenbaum LA, Dhalla NS (2005) Role of tumour necrosis factor-alpha and other cytokines in ischemia-reperfusion-induced injury in the heart. Exp Clin Cardiol 10:213–222PubMedPubMedCentral
104.
Zurück zum Zitat Skyschally A, Gent S, Amanakis G, Schulte C, Kleinbongard P, Heusch G (2015) Across-species transfer of protection by remote ischemic preconditioning with species-specific myocardial signal transduction by reperfusion injury salvage kinase and survival activating factor enhancement pathways. Circ Res 117:279–288. https://doi.org/10.1161/CIRCRESAHA.117.306878 CrossRefPubMed Skyschally A, Gent S, Amanakis G, Schulte C, Kleinbongard P, Heusch G (2015) Across-species transfer of protection by remote ischemic preconditioning with species-specific myocardial signal transduction by reperfusion injury salvage kinase and survival activating factor enhancement pathways. Circ Res 117:279–288. https://​doi.​org/​10.​1161/​CIRCRESAHA.​117.​306878 CrossRefPubMed
106.
Zurück zum Zitat Thielmann M, Kottenberg E, Kleinbongard P, Wendt D, Gedik N, Pasa S, Price V, Tsagakis K, Neuhauser M, Peters J, Jakob H, Heusch G (2013) Cardioprotective and prognostic effects of remote ischaemic preconditioning in patients undergoing coronary artery bypass surgery: a single-centre randomised, double-blind, controlled trial. Lancet 382:597–604. https://doi.org/10.1016/S0140-6736(13)61450-6 CrossRefPubMed Thielmann M, Kottenberg E, Kleinbongard P, Wendt D, Gedik N, Pasa S, Price V, Tsagakis K, Neuhauser M, Peters J, Jakob H, Heusch G (2013) Cardioprotective and prognostic effects of remote ischaemic preconditioning in patients undergoing coronary artery bypass surgery: a single-centre randomised, double-blind, controlled trial. Lancet 382:597–604. https://​doi.​org/​10.​1016/​S0140-6736(13)61450-6 CrossRefPubMed
107.
118.
Zurück zum Zitat Zhang T, Zhang Y, Cui M, Jin L, Wang Y, Lv F, Liu Y, Zheng W, Shang H, Zhang J, Zhang M, Wu H, Guo J, Zhang X, Hu X, Cao CM, Xiao RP (2016) CaMKII is a RIP3 substrate mediating ischemia- and oxidative stress-induced myocardial necroptosis. Nat Med 22:175–182. https://doi.org/10.1038/nm.4017 CrossRefPubMed Zhang T, Zhang Y, Cui M, Jin L, Wang Y, Lv F, Liu Y, Zheng W, Shang H, Zhang J, Zhang M, Wu H, Guo J, Zhang X, Hu X, Cao CM, Xiao RP (2016) CaMKII is a RIP3 substrate mediating ischemia- and oxidative stress-induced myocardial necroptosis. Nat Med 22:175–182. https://​doi.​org/​10.​1038/​nm.​4017 CrossRefPubMed
121.
Zurück zum Zitat Zhou Y, Zhang Y, Gao F, Guo F, Wang J, Cai W, Chen Y, Zheng J, Shi G (2010) N-n-butyl haloperidol iodide protects cardiac microvascular endothelial cells from hypoxia/reoxygenation injury by down-regulating Egr-1 expression. Cell Physiol Biochem 26:839–848. https://doi.org/10.1159/000323993 CrossRefPubMed Zhou Y, Zhang Y, Gao F, Guo F, Wang J, Cai W, Chen Y, Zheng J, Shi G (2010) N-n-butyl haloperidol iodide protects cardiac microvascular endothelial cells from hypoxia/reoxygenation injury by down-regulating Egr-1 expression. Cell Physiol Biochem 26:839–848. https://​doi.​org/​10.​1159/​000323993 CrossRefPubMed
122.
Zurück zum Zitat Zhu H, Bunn HF (1999) Oxygen sensing and signaling: impact on the regulation of physiologically important genes. Respir Physiol 115:239–247CrossRefPubMedCentral Zhu H, Bunn HF (1999) Oxygen sensing and signaling: impact on the regulation of physiologically important genes. Respir Physiol 115:239–247CrossRefPubMedCentral
Metadaten
Titel
Egr-1 functions as a master switch regulator of remote ischemic preconditioning-induced cardioprotection
verfasst von
M. Billah
A. Ridiandries
B. S. Rayner
U. K. Allahwala
A. Dona
L. M. Khachigian
R. Bhindi
Publikationsdatum
01.01.2020
Verlag
Springer Berlin Heidelberg
Erschienen in
Basic Research in Cardiology / Ausgabe 1/2020
Print ISSN: 0300-8428
Elektronische ISSN: 1435-1803
DOI
https://doi.org/10.1007/s00395-019-0763-9

Weitere Artikel der Ausgabe 1/2020

Basic Research in Cardiology 1/2020 Zur Ausgabe

„Übersichtlicher Wegweiser“: Lauterbachs umstrittener Klinik-Atlas ist online

17.05.2024 Klinik aktuell Nachrichten

Sie sei „ethisch geboten“, meint Gesundheitsminister Karl Lauterbach: mehr Transparenz über die Qualität von Klinikbehandlungen. Um sie abzubilden, lässt er gegen den Widerstand vieler Länder einen virtuellen Klinik-Atlas freischalten.

„Jeder Fall von plötzlichem Tod muss obduziert werden!“

17.05.2024 Plötzlicher Herztod Nachrichten

Ein signifikanter Anteil der Fälle von plötzlichem Herztod ist genetisch bedingt. Um ihre Verwandten vor diesem Schicksal zu bewahren, sollten jüngere Personen, die plötzlich unerwartet versterben, ausnahmslos einer Autopsie unterzogen werden.

Hirnblutung unter DOAK und VKA ähnlich bedrohlich

17.05.2024 Direkte orale Antikoagulanzien Nachrichten

Kommt es zu einer nichttraumatischen Hirnblutung, spielt es keine große Rolle, ob die Betroffenen zuvor direkt wirksame orale Antikoagulanzien oder Marcumar bekommen haben: Die Prognose ist ähnlich schlecht.

Schlechtere Vorhofflimmern-Prognose bei kleinem linken Ventrikel

17.05.2024 Vorhofflimmern Nachrichten

Nicht nur ein vergrößerter, sondern auch ein kleiner linker Ventrikel ist bei Vorhofflimmern mit einer erhöhten Komplikationsrate assoziiert. Der Zusammenhang besteht nach Daten aus China unabhängig von anderen Risikofaktoren.

Update Kardiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.