Novel perspectives on the PHD-HIF oxygen sensing pathway in cardioprotection mediated by IPC and RIPC

Frontiers in Physiology

Volumn 6, Issue MAY, 2015, Pages

  Martin Puig, Silvia ^a   Tello, Daniel ^b   Aragonés, Julián ^b  

^a CENTRO NACIONAL DE INVESTIGACIONES CARDIOVASCULARES CNIC   (Spain)

^b HOSPITAL UNIVERSITARIO SANTA CRISTINA   (Spain)

Author keywords

Heart; Hypoxia inducible factors; Ischemic preconditioning; PHD oxygen sensors; Remote ischemic preconditioning

Indexed keywords

NITRIC OXIDE; PROCOLLAGEN PROLINE 2 OXOGLUTARATE 4 DIOXYGENASE; PROTEIN KINASE;

CELLS BY BODY ANATOMY; HEART MUSCLE CELL; HEART MUSCLE METABOLISM; HEART PROTECTION; HUMAN; ISCHEMIC PRECONDITIONING; NONHUMAN; OXYGEN SENSING; REMOTE ISCHEMIC PRECONDITIONING; REPERFUSION INJURY; REVIEW; SIGNAL TRANSDUCTION; VASCULAR ENDOTHELIUM; VASCULAR REMODELING;

EID: 84930620735     PISSN: None     EISSN: 1664042X     Source Type: Journal    
DOI: 10.3389/fphys.2015.00137     Document Type: Review

References (84)

1. Albrecht, M., Zitta, K., Bein, B., Wennemuth, G., Broch, O., Renner, J., et al. (2013). Remote ischemic preconditioning regulates HIF-1alpha levels, apoptosis and inflammation in heart tissue of cardiosurgical patients: a pilot experimental study. Basic Res. Cardiol. 108, 314. doi: 10.1007/s00395-012-0314-0.
2. Andrukhiv, A., Costa, A. D., West, I. C., and Garlid, K. D. (2006). Opening mitoKATP increases superoxide generation from complex I of the electron transport chain. Am. J. Physiol. Heart. Circ. Physiol. 291, H2067-H2074. doi: 10.1152/ajpheart.00272.2006.
3. Aragones, J., Schneider, M., Van Geyte, K., Fraisl, P., Dresselaers, T., Mazzone, M., et al. (2008). Deficiency or inhibition of oxygen sensor Phd1 induces hypoxia tolerance by reprogramming basal metabolism. Nat. Genet. 40, 170-180. doi: 10.1038/ng.2007.62.
4. Bagchi, A. K., Sharma, A., Dhingra, S., Lehenbauer Ludke, A. R., Al-Shudiefat, A. A., and Singal, P. K. (2013). Interleukin-10 activates Toll-like receptor 4 and requires MyD88 for cardiomyocyte survival. Cytokine 61, 304-314. doi: 10.1016/j.cyto.2012.10.013.
5. Bolte, C. S., Liao, S., Gross, G. J., and Schultz Jel, J. (2007). Remote preconditioning-endocrine factors in organ protection against ischemic injury. Endocr. Metab. Immune Disord. Drug Targets 7, 167-175. doi: 10.2174/187153007781662585.
6. Burger, D., Xenocostas, A., and Feng, Q. P. (2009). Molecular basis of cardioprotection by erythropoietin. Curr. Mol. Pharmacol. 2, 56-69. doi: 10.2174/1874467210902010056.
7. Cai, Z., Luo, W., Zhan, H., and Semenza, G. L. (2013). Hypoxia-inducible factor 1 is required for remote ischemic preconditioning of the heart. Proc. Natl. Acad. Sci. U.S.A. 110, 17462-17467. doi: 10.1073/pnas.1317158110.
8. Cai, Z., and Semenza, G. L. (2005). PTEN activity is modulated during ischemia and reperfusion: involvement in the induction and decay of preconditioning. Circ. Res. 97, 1351-1359. doi: 10.1161/01.RES.0000195656.52760.30.
9. Cai, Z., Zhong, H., Bosch-Marce, M., Fox-Talbot, K., Wang, L., Wei, C., et al. (2008). Complete loss of ischaemic preconditioning-induced cardioprotection in mice with partial deficiency of HIF-1 alpha. Cardiovasc. Res. 77, 463-470. doi: 10.1093/cvr/cvm035.
10. Camici, G. G., Stallmach, T., Hermann, M., Hassink, R., Doevendans, P., Grenacher, B., et al. (2007). Constitutively overexpressed erythropoietin reduces infarct size in a mouse model of permanent coronary artery ligation. Methods Enzymol. 435, 147-155. doi: 10.1016/S0076-6879(07)35008-8.
11. Chan, S. Y., Zhang, Y. Y., Hemann, C., Mahoney, C. E., Zweier, J. L., and Loscalzo, J. (2009). MicroRNA-210 controls mitochondrial metabolism during hypoxia by repressing the iron-sulfur cluster assembly proteins ISCU1/2. Cell Metab. 10, 273-284. doi: 10.1016/j.cmet.2009.08.015.
12. Chen, Z., Li, Y., Zhang, H., Huang, P., and Luthra, R. (2010). Hypoxia-regulated microRNA-210 modulates mitochondrial function and decreases ISCU and COX10 expression. Oncogene 29, 4362-4368. doi: 10.1038/onc.2010.193.
13. Costa, A. D., Garlid, K. D., West, I. C., Lincoln, T. M., Downey, J. M., Cohen, M. V., et al. (2005). Protein kinase G transmits the cardioprotective signal from cytosol to mitochondria. Circ. Res. 97, 329-336. doi: 10.1161/01.RES.0000178451.08719.5b.
14. Costa, A. D., Pierre, S. V., Cohen, M. V., Downey, J. M., and Garlid, K. D. (2008). cGMP signalling in pre-and post-conditioning: the role of mitochondria. Cardiovasc Res. 77, 344-352. doi: 10.1093/cvr/cvm050.
15. Cummins, E. P., Berra, E., Comerford, K. M., Ginouves, A., Fitzgerald, K. T., Seeballuck, F., et al. (2006). Prolyl hydroxylase-1 negatively regulates IkappaB kinase-beta, giving insight into hypoxia-induced NFkappaB activity. Proc. Natl. Acad. Sci. U.S.A. 103, 18154-18159. doi: 10.1073/pnas.0602235103.
16. Czibik, G., Martinov, V., Ruusalepp, A., Sagave, J., Skare, O., and Valen, G. (2009). In vivo remote delivery of DNA encoding for hypoxia-inducible factor 1 alpha reduces myocardial infarct size. Clin. Transl. Sci. 2, 33-40. doi: 10.1111/j.1752-8062.2008.00077.x.
17. Davidson, S. M., Selvaraj, P., He, D., Boi-Doku, C., Yellon, R. L., Vicencio, J. M., et al. (2013). Remote ischaemic preconditioning involves signalling through the SDF-1alpha/CXCR4 signalling axis. Basic Res. Cardiol. 108, 377. doi: 10.1007/s00395-013-0377-6.
18. Dhingra, S., Bagchi, A. K., Ludke, A. L., Sharma, A. K., and Singal, P. K. (2011). Akt regulates IL-10 mediated suppression of TNFalpha-induced cardiomyocyte apoptosis by upregulating Stat3 phosphorylation. PLoS ONE 6:e25009. doi: 10.1371/journal.pone.0025009.
19. Dhingra, S., Sharma, A. K., Arora, R. C., Slezak, J., and Singal, P. K. (2009). IL-10 attenuates TNF-alpha-induced NF kappaB pathway activation and cardiomyocyte apoptosis. Cardiovasc. Res. 82, 59-66. doi: 10.1093/cvr/cvp040.
20. Divisova, J., Vavrinkova, H., Tutterova, M., Kazdova, L., and Meschisvili, E. (2001). Effect of ACE inhibitor captopril and L-arginine on the metabolism and on ischemia-reperfusion injury of the isolated rat heart. Physiol. Res. 50, 143-152.
21. Diwan, V., Kant, R., Jaggi, A. S., Singh, N., and Singh, D. (2008). Signal mechanism activated by erythropoietin preconditioning and remote renal preconditioning-induced cardioprotection. Mol. Cell. Biochem. 315, 195-201. doi: 10.1007/s11010-008-9808-3.
22. Eckle, T., Kohler, D., Lehmann, R., El Kasmi, K., and Eltzschig, H. K. (2008). Hypoxia-inducible factor-1 is central to cardioprotection: a new paradigm for ischemic preconditioning. Circulation 118, 166-175. doi: 10.1161/CIRCULATIONAHA.107.758516.
23. Eckle, T., Krahn, T., Grenz, A., Kohler, D., Mittelbronn, M., Ledent, C., et al. (2007). Cardioprotection by ecto-5'-nucleotidase (CD73) and A2B adenosine receptors. Circulation 115, 1581-1590. doi: 10.1161/CIRCULATIONAHA.106.669697.
24. Forbes, R. A., Steenbergen, C., and Murphy, E. (2001). Diazoxide-induced cardioprotection requires signaling through a redox-sensitive mechanism. Circ. Res. 88, 802-809.
25. Fraisl, P. (2013). Crosstalk between oxygen-and nitric oxide-dependent signaling pathways in angiogenesis. Exp. Cell Res. 319, 1331-1339. doi: 10.1016/j.yexcr.2013.02.010.
26. Fraisl, P., Aragones, J., and Carmeliet, P. (2009). Inhibition of oxygen sensors as a therapeutic strategy for ischaemic and inflammatory disease. Nat. Rev. Drug Discov. 8, 139-152. doi: 10.1038/nrd2761.
27. Gao, F., Gao, E., Yue, T. L., Ohlstein, E. H., Lopez, B. L., Christopher, T. A., et al. (2002). Nitric oxide mediates the antiapoptotic effect of insulin in myocardial ischemia-reperfusion: the roles of PI3-kinase, Akt, and endothelial nitric oxide synthase phosphorylation. Circulation 105, 1497-1502. doi: 10.1161/01.CIR.0000012529.00367.0F.
28. Garcia-Dorado, D., Garcia-del-Blanco, B., Otaegui, I., Rodriguez-Palomares, J., Pineda, V., Gimeno, F., et al. (2014). Intracoronary injection of adenosine before reperfusion in patients with ST-segment elevation myocardial infarction: a randomized controlled clinical trial. Int. J. Cardiol. 177, 935-941. doi: 10.1016/j.ijcard.2014.09.203.
29. Garcia-Dorado, D., Theroux, P., Duran, J. M., Solares, J., Alonso, J., Sanz, E., et al. (1992). Selective inhibition of the contractile apparatus. A new approach to modification of infarct size, infarct composition, and infarct geometry during coronary artery occlusion and reperfusion. Circulation 85, 1160-1174. doi: 10.1161/01.CIR.85.3.1160.
30. Gross, G. J., and Lockwood, S. F. (2004). Cardioprotection and myocardial salvage by a disodium disuccinate astaxanthin derivative (Cardax). Life Sci. 75, 215-224. doi: 10.1016/j.lfs.2003.12.006.
31. Guo, Y., Jones, W. K., Xuan, Y. T., Tang, X. L., Bao, W., Wu, W. J., et al. (1999). The late phase of ischemic preconditioning is abrogated by targeted disruption of the inducible NO synthase gene. Proc. Natl. Acad. Sci. U.S.A. 96, 11507-11512. doi: 10.1073/pnas.96.20.11507.
32. Halestrap, A. P., Clarke, S. J., and Javadov, S. A. (2004). Mitochondrial permeability transition pore opening during myocardial reperfusion-a target for cardioprotection. Cardiovasc. Res. 61, 372-385. doi: 10.1016/S0008-6363(03)00533-9.
33. Hausenloy, D. J., Tsang, A., Mocanu, M. M., and Yellon, D. M. (2005). Ischemic preconditioning protects by activating prosurvival kinases at reperfusion. Am. J. Physiol. Heart Circ. Physiol. 288, H971-H976. doi: 10.1152/ajpheart.00374.2004.
34. Hausenloy, D. J., and Yellon, D. M. (2007). Reperfusion injury salvage kinase signalling: taking a RISK for cardioprotection. Heart Fail. Rev. 12, 217-234. doi: 10.1007/s10741-007-9026-1.
35. Holscher, M., Silter, M., Krull, S., von Ahlen, M., Hesse, A., Schwartz, P., et al. (2011). Cardiomyocyte-specific prolyl-4-hydroxylase domain 2 knock out protects from acute myocardial ischemic injury. J. Biol. Chem. 286, 11185-11194. doi: 10.1074/jbc. M110.186809.
36. Hyvarinen, J., Hassinen, I. E., Sormunen, R., Maki, J. M., Kivirikko, K. I., Koivunen, P., et al. (2010). Hearts of hypoxia-inducible factor prolyl 4-hydroxylase-2 hypomorphic mice show protection against acute ischemia-reperfusion injury. J. Biol. Chem. 285, 13646-13657. doi: 10.1074/jbc. M109.084855.
37. Jones, S. P., Girod, W. G., Palazzo, A. J., Granger, D. N., Grisham, M. B., Jourd'Heuil, D., et al. (1999). Myocardial ischemia-reperfusion injury is exacerbated in absence of endothelial cell nitric oxide synthase. Am. J. Physiol. 276(5 Pt 2), H1567-1573.
38. Jung, F., Palmer, L. A., Zhou, N., and Johns, R. A. (2000). Hypoxic regulation of inducible nitric oxide synthase via hypoxia inducible factor-1 in cardiac myocytes. Circ. Res. 86, 319-325. doi: 10.1161/01.RES.86.3.319.
39. Kalakech, H., Tamareille, S., Pons, S., Godin-Ribuot, D., Carmeliet, P., Furber, A., et al. (2013). Role of hypoxia inducible factor-1alpha in remote limb ischemic preconditioning. J. Mol. Cell. Cardiol. 65, 98-104. doi: 10.1016/j.yjmcc.2013.10.001.
40. Kant, R., Diwan, V., Jaggi, A. S., Singh, N., and Singh, D. (2008). Remote renal preconditioning-induced cardioprotection: a key role of hypoxia inducible factor-prolyl 4-hydroxylases. Mol. Cell. Biochem. 312, 25-31. doi: 10.1007/s11010-008-9717-5.
41. Kapitsinou, P. P., Sano, H., Michael, M., Kobayashi, H., Davidoff, O., Bian, A., et al. (2014). Endothelial HIF-2 mediates protection and recovery from ischemic kidney injury. J. Clin. Invest. 124, 2396-2409. doi: 10.1172/JCI69073.
42. Kerkela, R., Karsikas, S., Szabo, Z., Serpi, R., Magga, J., Gao, E., et al. and (2013). Activation of hypoxia response in endothelial cells contributes to ischemic cardioprotection. Mol. Cell. Biol. 33, 3321-3329. doi: 10.1128/MCB.00432-13.
43. Kevin, L. G., Camara, A. K., Riess, M. L., Novalija, E., and Stowe, D. F. (2003). Ischemic preconditioning alters real-time measure of O2 radicals in intact hearts with ischemia and reperfusion. Am. J. Physiol. Heart Circ. Physiol. 284, H566-H574. doi: 10.1152/ajpheart.00711.2002.
44. Kharbanda, R. K., Mortensen, U. M., White, P. A., Kristiansen, S. B., Schmidt, M. R., Hoschtitzky, J. A., et al. (2002). Transient limb ischemia induces remote ischemic preconditioning in vivo. Circulation 106, 2881-2883. doi: 10.1161/01.CIR.0000043806.51912.9B.
45. Kim, J. W., Tchernyshyov, I., Semenza, G. L., and Dang, C. V. (2006). HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab. 3, 177-185. doi: 10.1016/j.cmet.2006.02.002.
46. Kinzenbaw, D. A., Chu, Y., Pena Silva, R. A., Didion, S. P., and Faraci, F. M. (2013). Interleukin-10 protects against aging-induced endothelial dysfunction. Physiol. Rep. 1, e00149. doi: 10.1002/phy2.149.
47. Krishnan, J., Suter, M., Windak, R., Krebs, T., Felley, A., Montessuit, C., et al. (2009). Activation of a HIF1alpha-PPARgamma axis underlies the integration of glycolytic and lipid anabolic pathways in pathologic cardiac hypertrophy. Cell Metab. 9, 512-524. doi: 10.1016/j.cmet.2009.05.005.
48. Lando, D., Goman, J. J., Whitelaw, M. L., and Peet, D. J. (2003). Oxygen-dependent regulation of hypoxia-inducible factors by prolyl and asparaginyl hydroxylation. Eur. J. Biochem. 270, 781-790. doi: 10.1046/j.1432-1033.2003.03445.x.
49. Lei, L., Mason, S., Liu, D., Huang, Y., Marks, C., Hickey, R., et al. (2008). Hypoxia-inducible factor-dependent degeneration, failure, and malignant transformation of the heart in the absence of the von Hippel-Lindau protein. Mol. Cell. Biol. 28, 3790-3803. doi: 10.1128/MCB.01580-07.
50. Lu, C. W., Lin, S. C., Chen, K. F., Lai, Y. Y., and Tsai, S. J. (2008). Induction of pyruvate dehydrogenase kinase-3 by hypoxia-inducible factor-1 promotes metabolic switch and drug resistance. J. Biol. Chem. 283, 28106-28114. doi: 10.1074/jbc. M803508200.
51. Lund, A., Lundby, C., and Olsen, N. V. (2014). High-dose erythropoietin for tissue protection. Eur. J. Clin. Invest. 44, 1230-1238. doi: 10.1111/eci.12357.
52. Martin-Puig, S., Wang, Z., and Chien, K. R. (2008). Lives of a heart cell: tracing the origins of cardiac progenitors. Cell Stem Cell 2, 320-331. doi: 10.1016/j.stem.2008.03.010.
53. Marzo, F., Lavorgna, A., Coluzzi, G., Santucci, E., Tarantino, F., Rio, T., et al. (2008). Erythropoietin in heart and vessels: focus on transcription and signalling pathways. J. Thromb. Thrombolysis 26, 183-187. doi: 10.1007/s11239-008-0212-3.
54. Mastromarino, V., Musumeci, M. B., Conti, E., Tocci, G., and Volpe, M. (2013). Erythropoietin in cardiac disease: effective or harmful? J. Cardiovasc. Med. (Hagerstown) 14, 870-878. doi: 10.2459/JCM.0b013e328362c6ae.
55. Minamishima, Y. A., Moslehi, J., Bardeesy, N., Cullen, D., Bronson, R. T., and Kaelin, W. G. Jr. (2008). Somatic inactivation of the PHD2 prolyl hydroxylase causes polycythemia and congestive heart failure. Blood 111, 3236-3244. doi: 10.1182/blood-2007-10-117812.
56. Minamishima, Y. A., Moslehi, J., Padera, R. F., Bronson, R. T., Liao, R., and Kaelin, W. G. Jr. (2009). A feedback loop involving the Phd3 prolyl hydroxylase tunes the mammalian hypoxic response in vivo. Mol. Cell. Biol. 29, 5729-5741. doi: 10.1128/MCB.00331-09.
57. Miro-Murillo, M., Elorza, A., Soro-Arnaiz, I., Albacete-Albacete, L., Ordonez, A., Balsa, E., et al. (2011). Acute Vhl gene inactivation induces cardiac HIF-dependent erythropoietin gene expression. PLoS ONE 6:e22589. doi: 10.1371/journal.pone.0022589.
58. Mocanu, M. M., and Yellon, D. M. (2007). PTEN, the Achilles' heel of myocardial ischaemia/reperfusion injury? Br. J. Pharmacol. 150, 833-838. doi: 10.1038/sj.bjp.0707155.
59. Murphy, E., and Steenbergen, C. (2008). Mechanisms underlying acute protection from cardiac ischemia-reperfusion injury. Physiol. Rev. 88, 581-609. doi: 10.1152/physrev.00024.2007.
60. Murry, C. E., Jennings, R. B., and Reimer, K. A. (1986). Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74, 1124-1136. doi: 10.1161/01.CIR.74.5.1124.
61. Ong, S. B., Hall, A. R., Dongworth, R. K., Kalkhoran, S., Pyakurel, A., Scorrano, L., et al. (2014a). Akt protects the heart against ischaemia-reperfusion injury by modulating mitochondrial morphology. Thromb. Haemost. 113, 513-521. doi: 10.1160/TH14-07-0592.
62. Ong, S. G., Lee, W. H., Theodorou, L., Kodo, K., Lim, S. Y., Shukla, D. H., et al. (2014b). HIF-1 reduces ischaemia-reperfusion injury in the heart by targeting the mitochondrial permeability transition pore. Cardiovasc. Res. 104, 24-36. doi: 10.1093/cvr/cvu172.
63. Papandreou, I., Cairns, R. A., Fontana, L., Lim, A. L., and Denko, N. C. (2006). HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. Cell Metab. 3, 187-197. doi: 10.1016/j.cmet.2006.01.012.
64. Park, S. S., Zhao, H., Mueller, R. A., and Xu, Z. (2006). Bradykinin prevents reperfusion injury by targeting mitochondrial permeability transition pore through glycogen synthase kinase 3beta. J. Mol. Cell. Cardiol. 40, 708-716. doi: 10.1016/j.yjmcc.2006.01.024.
65. Piper, H. M., Kasseckert, S., and Abdallah, Y. (2006). The sarcoplasmic reticulum as the primary target of reperfusion protection. Cardiovasc. Res. 70, 170-173. doi: 10.1016/j.cardiores.2006.03.010.
66. Randhawa, P. K., and Jaggi, A. S. (2014). TRPV1 and TRPV4 channels: Potential therapeutic targets for ischemic conditioning-induced cardioprotection. Eur. J. Pharmacol. 746C, 180-185. doi: 10.1016/j.ejphar.2014.11.010.
67. Safran, M., and Kaelin, W. G. Jr. (2003). HIF hydroxylation and the mammalian oxygen-sensing pathway. J. Clin. Invest. 111, 779-783. doi: 10.1172/JCI200318181.
68. Schneider, M., Van Geyte, K., Fraisl, P., Kiss, J., Aragones, J., Mazzone, M., et al. (2010). Loss or silencing of the PHD1 prolyl hydroxylase protects livers of mice against ischemia/reperfusion injury. Gastroenterology 138, 1143-54.e1-2. doi: 10.1053/j.gastro.2009.09.057.
69. Schofield, C. J., and Ratcliffe, P. J. (2004). Oxygen sensing by HIF hydroxylases. Nat. Rev. Mol. Cell. Biol. 5, 343-354. doi: 10.1038/nrm1366.
70. Semenza, G. L. (2007). Life with oxygen. Science 318, 62-64. doi: 10.1126/science.1147949.
71. Semenza, G. L., Roth, P. H., Fang, H. M., and Wang, G. L. (1994). Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1. J. Biol. Chem. 269, 23757-23763.
72. Shahid, M., Tauseef, M., Sharma, K. K., and Fahim, M. (2008). Brief femoral artery ischaemia provides protection against myocardial ischaemia-reperfusion injury in rats: the possible mechanisms. Exp. Physiol. 93, 954-968. doi: 10.1113/expphysiol.2007.041442.
73. Singh, M., Shah, T., Khosla, K., Singh, P., Molnar, J., Khosla, S., et al. (2012). Safety and efficacy of intracoronary adenosine administration in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention: a meta-analysis of randomized controlled trials. Ther. Adv. Cardiovasc. Dis. 6, 101-114. doi: 10.1177/1753944712446670.
74. Takeda, K., Cowan, A., and Fong, G. H. (2007). Essential role for prolyl hydroxylase domain protein 2 in oxygen homeostasis of the adult vascular system. Circulation 116, 774-781. doi: 10.1161/CIRCULATIONAHA.107.701516.
75. Talan, M. I., and Latini, R. (2013). Myocardial infarction: cardioprotection by erythropoietin. Methods Mol. Biol. 982, 265-302. doi: 10.1007/978-1-62703-308-4_17.
76. Tello, D., Balsa, E., Acosta-Iborra, B., Fuertes-Yebra, E., Elorza, A., Ordonez, A., et al. (2011). Induction of the mitochondrial NDUFA4L2 protein by HIF-1alpha decreases oxygen consumption by inhibiting Complex I activity. Cell Metab. 14, 768-779. doi: 10.1016/j.cmet.2011.10.008.
77. Tsang, A., Hausenloy, D. J., Mocanu, M. M., and Yellon, D. M. (2004). Postconditioning: a form of "modified reperfusion" protects the myocardium by activating the phosphatidylinositol 3-kinase-Akt pathway. Circ. Res. 95, 230-232. doi: 10.1161/01.RES.0000138303.76488.fe.
78. Ueda, K., Takano, H., Niitsuma, Y., Hasegawa, H., Uchiyama, R., Oka, T., et al. (2010). Sonic hedgehog is a critical mediator of erythropoietin-induced cardiac protection in mice. J. Clin. Invest. 120, 2016-2029. doi: 10.1172/JCI39896.
79. Vavrínková, H., Tutterová, M., Stopka, P., Divisová, J., Kazdová, L., and Drahota, Z. (2001). The effect of captopril on nitric oxide formation and on generation of radical forms of mitochondrial respiratory chain compounds in ischemic rat heart. Physiol. Res. 50, 481-489.
80. Verma, S. K., Krishnamurthy, P., Barefield, D., Singh, N., Gupta, R., Lambers, E., et al. (2012). Interleukin-10 treatment attenuates pressure overload-induced hypertrophic remodeling and improves heart function via signal transducers and activators of transcription 3-dependent inhibition of nuclear factor-kappaB. Circulation 126, 418-429. doi: 10.1161/CIRCULATIONAHA.112.112185.
81. Yao, Z., Tong, J., Tan, X., Li, C., Shao, Z., Kim, W. C., et al. (1999). Role of reactive oxygen species in acetylcholine-induced preconditioning in cardiomyocytes. Am. J. Physiol. 277(6 Pt 2), H2504-H2509.
82. Zhong, L., D'Urso, A., Toiber, D., Sebastian, C., Henry, R. E., Vadysirisack, D. D., et al. (2010). The histone deacetylase Sirt6 regulates glucose homeostasis via Hif1alpha. Cell 140, 280-293. doi: 10.1016/j.cell.2009.12.041.
83. Zhou, B., Honor, L. B., He, H., Ma, Q., Oh, J. H., Butterfield, C., et al. (2011). Adult mouse epicardium modulates myocardial injury by secreting paracrine factors. J. Clin. Invest. 121, 1894-1904. doi: 10.1172/JCI45529.
84. Ziegler, M., Elvers, M., Baumer, Y., Leder, C., Ochmann, C., Schonberger, T., et al. (2012). The bispecific SDF1-GPVI fusion protein preserves myocardial function after transient ischemia in mice. Circulation 125, 685-696. doi: 10.1161/CIRCULATIONAHA.111.070508.