Signaling Pathways in Cardiac Myocyte Apoptosis

BioMed Research International

Volumn 2016, Issue , 2016, Pages

  Xia, Peng ^a   Liu, Yuening ^a   Cheng, Zhaokang ^a  

^a WASHINGTON STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CALCINEURIN; CYCLIC AMP DEPENDENT PROTEIN KINASE; G PROTEIN COUPLED RECEPTOR; GLYCOGEN SYNTHASE KINASE 3; GUANOSINE TRIPHOSPHATASE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTEGRIN; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; NOTCH RECEPTOR; PH DOMAIN LEUCINE RICH REPEAT PROTEIN PHOSPHATASE; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PHOSPHOPROTEIN PHOSPHATASE; PROTEIN KINASE B; PROTEIN KINASE C; PROTEIN KINASE PIM 1; SERRATE JAGGED PROTEIN; STRESS ACTIVATED PROTEIN KINASE; TRANSCRIPTION FACTOR FKHR; TUMOR NECROSIS FACTOR; UNCLASSIFIED DRUG;

APOPTOSIS; CARDIAC MUSCLE CELL; CELL CYCLE REGULATION; HEART DISEASE; HEART FUNCTION; HUMAN; NONHUMAN; PHASE 2 CLINICAL TRIAL (TOPIC); RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SIGNAL TRANSDUCTION; ANIMAL; HEART DISEASES; METABOLISM; PATHOLOGY;

ANIMALS; APOPTOSIS; HEART DISEASES; HUMANS; MYOCYTES, CARDIAC; SIGNAL TRANSDUCTION;

EID: 85008925639     PISSN: 23146133     EISSN: 23146141     Source Type: Journal    
DOI: 10.1155/2016/9583268     Document Type: Review

References (304)

1. J. U. Schweichel and H. J. Merker, "The morphology of various types of cell death in prenatal tissues," Teratology, vol. 7, no. 3, pp. 253-266, 1973.
2. J. F. Kerr, A. H. Wyllie, and A. R. Currie, "Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics," British Journal of Cancer, vol. 26, no. 4, pp. 239-257, 1972.
3. L. Galluzzi, J. M. Bravo-San Pedro, I. Vitale et al., "Essential versus accessory aspects of cell death: recommendations of the NCCD 2015," Cell Death and Differentiation, vol. 22, no. 1, pp. 58-73, 2015.
4. Y. Liu and B. Levine, "Autosis andautophagic cell death: thedark side of autophagy," Cell Death and Differentiation, vol. 22, no. 3, pp. 367-376, 2015.
5. T. Vanden Berghe, A. Linkermann, S. Jouan-Lanhouet, H. Walczak, and P. Vandenabeele, "Regulated necrosis: the expanding network of non-apoptotic cell death pathways," Nature Reviews Molecular Cell Biology, vol. 15, no. 2, pp. 135-147, 2014.
6. A. Haunstetter and S. Izumo, "Apoptosis: basicmechanisms and implications for cardiovascular disease," Circulation Research, vol. 82, no. 11, pp. 1111-1129, 1998.
7. M. Watanabe, A. Choudhry, M. Berlan et al., "Developmental remodeling and shortening of the cardiac outflow tract involves myocyte programmed cell death," Development, vol. 125, no. 19, pp. 3809-3820, 1998.
8. M. Watanabe, A. Jafri, and S. A. Fisher, "Apoptosis is required for the proper formation of the ventriculo-arterial connections," Developmental Biology, vol. 240, no. 1, pp. 274-288, 2001.
9. G. Kung, K. Konstantinidis, and R. N. Kitsis, "Programmed necrosis, not apoptosis, in the heart," Circulation Research, vol. 108, no. 8, pp. 1017-1036, 2011.
10. M. Chiong, Z. V. Wang, Z. Pedrozo et al., "Cardiomyocyte death: mechanisms and translational implications," Cell Death and Disease, vol. 2, no. 12, article e244, 2011.
11. M. A. Sussman, M. Völkers, K. Fischer et al., "Myocardial AKT: the omnipresent nexus," Physiological Reviews, vol. 91, no. 3, pp. 1023-1070, 2011.
12. Y. Fujio, T. Nguyen, D. Wencker, R. N. Kitsis, and K. Walsh, "Akt promotes survival of cardiomyocytes in vitro and protects against ischemia-reperfusion injury in mouse heart," Circulation, vol. 101, no. 6, pp. 660-667, 2000.
13. R. Aikawa, M. Nawano, Y. Gu et al., "Insulin prevents cardiomyocytes from oxidative stress-induced apoptosis through activation of PI3 kinase/Akt," Circulation, vol. 102, no. 23, pp. 2873-2879, 2000.
14. T. Matsui, J. Tao, F. del Monte et al., "Akt activation preserves cardiac function and prevents injury after transient cardiac ischemia in vivo," Circulation, vol. 104, no. 3, pp. 330-335, 2001.
15. T. Matsui, N. Li, J. C. Wu et al., "Phenotypic spectrumcaused by transgenic overexpression of activated Akt in the heart," Journal of Biological Chemistry, vol. 277, no. 25, pp. 22896-22901, 2002.
16. T. Nagoshi, T. Matsui, T. Aoyama et al., "PI3K rescues the detrimental effects of chronic Akt activation in the heart during ischemia/reperfusion injury," The Journal of Clinical Investigation, vol. 115, no. 8, pp. 2128-2138, 2005.
17. D. Camper-Kirby, S. Welch, A. Walker et al., "Myocardial Akt activation and gender: increased nuclear activity in females versus males," Circulation Research, vol. 88, no. 10, pp. 1020-1027, 2001.
18. I. Shiraishi, J. Melendez, Y. Ahn et al., "Nuclear targeting of Akt enhances kinase activity and survival of cardiomyocytes," Circulation Research, vol. 94, no. 7, pp. 884-891, 2004.
19. T. Kato, J. Muraski, Y. Chen et al., "Atrial natriuretic peptide promotes cardiomyocyte survival by cGMP-dependent nuclear accumulation of zyxin and Akt," Journal of Clinical Investigation, vol. 115, no. 10, pp. 2716-2730, 2005.
20. J. A. Muraski, M. Rota, Y. Misao et al., "Pim-1 regulates cardiomyocyte survival downstream of Akt," Nature Medicine, vol. 13, no. 12, pp. 1467-1475, 2007.
21. S. Miyamoto, A. N. Murphy, and J. H. Brown, "Akt mediates mitochondrial protection in cardiomyocytes through phosphorylation of mitochondrial hexokinase-II," Cell Death & Differentiation, vol. 15, no. 3, pp. 521-529, 2008.
22. D. J. Roberts, V. P. Tan-Sah, J. M. Smith, and S. Miyamoto, "Akt phosphorylates HK-II at Thr-473 and increases mitochondrial HK-II association to protect cardiomyocytes," Journal of Biological Chemistry, vol. 288, no. 33, pp. 23798-23806, 2013.
23. B. DeBosch, N. Sambandam, C. Weinheimer, M. Courtois, and A. J. Muslin, "Akt2 regulates cardiacmetabolism and cardiomyocyte survival," Journal of Biological Chemistry, vol. 281, no. 43, pp. 32841-32851, 2006.
24. H. Tong, W. Chen, C. Steenbergen, and E. Murphy, "Ischemic preconditioning activates phosphatidylinositol-3-kinase upstream of protein kinase C," Circulation Research, vol. 87, no. 4, pp. 309-315, 2000.
25. T. Uchiyama, R.M. Engelman, N. Maulik, and D. K. Das, "Role of Akt signaling in mitochondrial survival pathway triggered by hypoxic preconditioning," Circulation, vol. 109, no. 24, pp. 3042-3049, 2004.
26. R. D. Patten, I. Pourati, M. J. Aronovitz et al., "17β-Estradiol reduces cardiomyocyte apoptosis in vivo and in vitro via activation of phospho-inositide-3 kinase/Akt signaling," Circulation Research, vol. 95, no. 7, pp. 692-699, 2004.
27. S. Negoro, H. Oh, E. Tone et al., "Glycoprotein 130 regulates cardiac myocyte survival in doxorubicin-induced apoptosis through phosphatidylinositol 3-kinase/Akt phosphorylation and Bcl-xL/caspase-3 interaction," Circulation, vol. 103, no. 4, pp. 555-561, 2001.
28. R. Fukazawa, T. A. Miller, Y. Kuramochi et al., "Neuregulin-1 protects ventricular myocytes from anthracycline-induced apoptosis via erb B4-dependent activation of PI3-kinase/Akt," Journal of Molecular and Cellular Cardiology, vol. 35, no. 12, pp. 1473-1479, 2003.
29. H. Yin, L. Chao, and J. Chao, "Adrenomedullin protects against myocardial apoptosis after ischemia/reperfusion through activation of Akt-GSK signaling," Hypertension, vol. 43, no. 1, pp. 109-116, 2004.
30. H. Yin, L. Chao, and J. Chao, "Kallikrein/kinin protects against myocardial apoptosis after ischemia/reperfusion via Akt-glycogen synthase kinase-3 and Akt-bad·14-3-3 signaling pathways," The Journal of Biological Chemistry, vol. 280, no. 9, pp. 8022-8030, 2005.
31. M. Jamnicki-Abegg, D. Weihrauch, P. S. Pagel et al., "Isoflurane inhibits cardiac myocyte apoptosis during oxidative and inflammatory stress by activating Akt and enhancing Bcl-2 expression," Anesthesiology, vol. 103, no. 5, pp. 1006-1014, 2005.
32. H.-O. Jun, D.-H. Kim, S.-W. Lee et al., "Clusterin protects H9c2 cardiomyocytes from oxidative stress-induced apoptosis via Akt/GSK-3β signaling pathway," Experimental and Molecular Medicine, vol. 43, no. 1, pp. 53-61, 2011.
33. H.-J. Hong, J.-C. Liu, P.-Y. Chen, J.-J. Chen, P. Chan, and T.-H. Cheng, "Tanshinone IIA prevents doxorubicin-induced cardiomyocyte apoptosis through Akt-dependent pathway," International Journal of Cardiology, vol. 157, no. 2, pp. 174-179, 2012.
34. Y.-L. Chen, S.-H. Loh, J.-J. Chen, and C.-S. Tsai, "Urotensin II prevents cardiomyocyte apoptosis induced by doxorubicin via Akt and ERK," European Journal of Pharmacology, vol. 680, no. 1-3, pp. 88-94, 2012.
35. Y. Kitamura, M. Koide, Y. Akakabe et al., "Manipulation of cardiac phosphatidylinositol 3-kinase (PI3K)/Akt signaling by apoptosis regulator throughmodulating IAP expression (ARIA) regulates cardiomyocyte death during doxorubicin-induced cardiomyopathy," Journal of Biological Chemistry, vol. 289, no. 5, pp. 2788-2800, 2014.
36. Y. Ying, H. Zhu, Z. Liang, X. Ma, and S. Li, "GLP1 protects cardiomyocytes from palmitate-induced apoptosis via Akt/GSK3b/b-catenin pathway," Journal of Molecular Endocrinology, vol. 55, no. 3, pp. 245-262, 2015.
37. G. Schwartzbauer and J. Robbins, "The tumor suppressor gene PTEN can regulate cardiac hypertrophy and survival," Journal of Biological Chemistry, vol. 276, no. 38, pp. 35786-35793, 2001.
38. H. Ruan, J. Li, S. Ren et al., "Inducible and cardiac specific PTEN inactivation protects ischemia/reperfusion injury," Journal of Molecular and Cellular Cardiology, vol. 46, no. 2, pp. 193-200, 2009.
39. R. Seqqat, X. Guo, K. Rafiq et al., "Beta1-adrenergic receptors promote focal adhesion signaling downregulation andmyocyte apoptosis in acute volume overload," Journal of Molecular and Cellular Cardiology, vol. 53, no. 2, pp. 240-249, 2012.
40. R. B. Chagpar, P. H. Links, M. C. Pastor et al., "Direct positive regulation of PTEN by the p85 subunit of phosphatidylinositol 3-kinase," Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 12, pp. 5471-5476, 2010.
41. X. Zhu, Z.-H. Shao, C. Li et al., "TAT-protein blockade during ischemia/reperfusion reveals critical role for p85 PI3K-PTEN interaction in cardiomyocyte injury," PLoS ONE, vol. 9, no. 4, Article ID e95622, 2014.
42. J. Chang, M. Xie, V. R. Shah et al., "Activation of Rhoassociated coiled-coil protein kinase 1 (ROCK-1) by caspase-3 cleavage plays an essential role in cardiac myocyte apoptosis," Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 39, pp. 14495-14500, 2006.
43. S. Miyamoto, N. H. Purcell, J. M. Smith et al., "PHLPP-1 negatively regulates Akt activity and survival in the heart," Circulation Research, vol. 107, no. 4, pp. 476-484, 2010.
44. Y. Xing, W. Sun, Y. Wang, F. Gao, and H. Ma, "Mutual inhibition of insulin signaling and PHLPP-1 determines cardioprotective efficiency of Akt in aged heart," Aging, vol. 8, no. 5, pp. 873-888, 2016.
45. M. H. Gao, A. Miyanohara, J. R. Feramisco, and T. Tang, "Activation of PH-domain leucine-rich protein phosphatase 2 (PHLPP2) by agonist stimulation in cardiac myocytes expressing adenylyl cyclase type 6," Biochemical and Biophysical Research Communications, vol. 384, no. 2, pp. 193-198, 2009.
46. H. Tong, K. Imahashi, C. Steenbergen, and E. Murphy, "Phosphorylation of glycogen synthase kinase-3β during preconditioning through a phosphatidylinositol-3-kinase-dependent pathway is cardioprotective," Circulation Research, vol. 90, no. 4, pp. 377-379, 2002.
47. S. Hirotani, P. Zhai, H. Tomita et al., "Inhibition of glycogen synthase kinase 3β during heart failure is protective," Circulation Research, vol. 101, no. 11, pp. 1164-1174, 2007.
48. P. Zhai, S. Gao, E. Holle et al., "Glycogen synthase kinase-3α reduces cardiac growth and pressure overload-induced cardiac hypertrophy by inhibition of extracellular signal-regulated kinases," The Journal of Biological Chemistry, vol. 282, no. 45, pp. 33181-33191, 2007.
49. K. C. Woulfe, E. Gao, H. Lal et al., "Glycogen synthase kinase-3β regulates post-myocardial infarction remodeling and stress-induced cardiomyocyte proliferation in vivo," Circulation Research, vol. 106, no. 10, pp. 1635-1645, 2010.
50. H. Lal, J. Zhou, F. Ahmad et al., "Glycogen synthase kinase-3α limits ischemic injury, cardiac rupture, post-myocardial infarction remodeling and death," Circulation, vol. 125, no. 1, pp. 65-75, 2012.
51. F. Ahmad, H. Lal, J. Zhou et al., "Cardiomyocyte-specific deletion of Gsk3α mitigates post-myocardial infarction remodeling, contractile dysfunction, and heart failure," Journal of the American College of Cardiology, vol. 64, no. 7, pp. 696-706, 2014.
52. J. Zhou, F. Ahmad, S. Parikh et al., "Loss of adult cardiac myocyte GSK-3 leads to mitotic catastrophe resulting in fatal dilated cardiomyopathy," Circulation Research, vol. 118, no. 8, pp. 1208-1222, 2016.
53. J. A. Muraski, K. M. Fischer, W. Wu et al., "Pim-1 kinase antagonizes aspects of myocardial hypertrophy and compensation to pathological pressure overload," Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 37, pp. 13889-13894, 2008.
54. G. A. Borillo, M. Mason, P. Quijada et al., "Pim-1 kinase protects mitochondrial integrity in cardiomyocytes," Circulation Research, vol. 106, no. 7, pp. 1265-1274, 2010.
55. C. Penna, M. G. Perrelli, S. Raimondo et al., "Postconditioning induces an anti-apoptotic effect and preserves mitochondrial integrity in isolated rat hearts," Biochimica et Biophysica Acta (BBA)-Bioenergetics, vol. 1787, no. 7, pp. 794-801, 2009.
56. R. G. Katare, A. Caporali, A. Oikawa, M. Meloni, C. Emanuel, and P. Madeddu, "Vitamin B1 analog benfotiamine prevents diabetes-induced diastolic dysfunction and heart failure through Akt/Pim-1-mediated survival pathway," Circulation: Heart Failure, vol. 3, no. 2, pp. 294-305, 2010.
57. X. Zhang, N. Tang, T. J. Hadden, and A. K. Rishi, "Akt, FoxO and regulation of apoptosis," Biochimica et Biophysica Acta, vol. 1813, no. 11, pp. 1978-1986, 2011.
58. A. Sengupta, J. D. Molkentin, and K. E. Yutzey, "FoxO transcription factors promote autophagy in cardiomyocytes," Journal of Biological Chemistry, vol. 284, no. 41, pp. 28319-28331, 2009.
59. H. J. Evans-Anderson, C. M. Alfieri, and K. E. Yutzey, "Regulation of cardiomyocyte proliferation and myocardial growth during development by FOXO transcription factors," Circulation Research, vol. 102, no. 6, pp. 686-694, 2008.
60. A. Sengupta, J. D. Molkentin, J.-H. Paik, R. A. DePinho, and K. E. Yutzey, "FoxO transcription factors promote cardiomyocyte survival upon induction of oxidative stress," The Journal of Biological Chemistry, vol. 286, no. 9, pp. 7468-7478, 2011.
61. D. Shao, P. Zhai, D. P. Del Re et al., "A functional interaction between Hippo-YAP signalling and FoxO1 mediates the oxidative stress response," Nature Communications, vol. 5, article no. 3315, 2014.
62. D. Lu, J. Liu, J. Jiao et al., "Transcription factor Foxo3a prevents apoptosis by regulating calciumthrough the apoptosis repressor with caspase recruitment domain," Journal of Biological Chemistry, vol. 288, no. 12, pp. 8491-8504, 2013.
63. F. Boal, A. Timotin, J. Roumegoux et al., "Apelin-13 administration protects against ischaemia/reperfusion-mediated apoptosis through the FoxO1 pathway in high-fat diet-induced obesity," British Journal of Pharmacology, vol. 173, no. 11, pp. 1850-1863, 2016.
64. R. Aikawa, I. Komuro, T. Yamazaki et al., "Oxidative stress activates extracellular signal-regulated kinases through Src and Ras in cultured cardiac myocytes of neonatal rats," The Journal of Clinical Investigation, vol. 100, no. 7, pp. 1813-1821, 1997.
65. W. Zhu, Y. Zou, R. Aikawa et al., "MAPK superfamily plays an important role in daunomycin-induced apoptosis of cardiac myocytes," Circulation, vol. 100, no. 20, pp. 2100-2107, 1999.
66. T.-L. Yue, C. Wang, J.-L. Gu et al., "Inhibition of extracellular signal-regulated kinase enhances ischemia/reoxygenationinduced apoptosis in cultured cardiacmyocytes and exaggerates reperfusion injury in isolated perfused heart," Circulation Research, vol. 86, no. 6, pp. 692-699, 2000.
67. J. Liu, W. Mao, B. Ding, and C.-S. Liang, "ERKs/p53 signal transduction pathway is involved in doxorubicin-induced apoptosis in H9c2 cells and cardiomyocytes," American Journal of Physiology-Heart and Circulatory Physiology, vol. 295, no. 5, pp. H1956-H1965, 2008.
68. I. S. Harris, S. Zhang, I. Treskov, A. Kovacs, C. Weinheimer, and A. J. Muslin, "Raf-1 kinase is required for cardiac hypertrophy and cardiomyocyte survival in response to pressure overload," Circulation, vol. 110, no. 6, pp. 718-723, 2004.
69. O. Yamaguchi, T. Watanabe, K. Nishida et al., "Cardiac-specific disruption of the c-raf-1 gene induces cardiac dysfunction and apoptosis," The Journal of Clinical Investigation, vol. 114, no. 7, pp. 937-943, 2004.
70. D. J. Lips, O. F. Bueno, B. J. Wilkins et al., "MEK1-ERK2 signaling pathway protects myocardium from ischemic injury in vivo," Circulation, vol. 109, no. 16, pp. 1938-1941, 2004.
71. S. Ulm, W. Liu, M. Zi et al., "Targeted deletion of ERK2 in cardiomyocytes attenuates hypertrophic response but provokes pathological stress induced cardiac dysfunction," Journal of Molecular and Cellular Cardiology, vol. 72, pp. 104-116, 2014.
72. Y. Huang, C. D. Wright, C. L. Merkwan et al., "An α1Aadrenergic-extracellular signal-regulated kinase survival signaling pathway in cardiac myocytes," Circulation, vol. 115, no. 6, pp. 763-772, 2007.
73. D. Zhang, L. Zhu, C. Li et al., "Sialyltransferase7A, a Klf4-responsive gene, promotes cardiomyocyte apoptosis during myocardial infarction," Basic Research in Cardiology, vol. 110, no. 3, 2015.
74. D. Hreniuk, M. Garay, W. Gaarde, B. P. Monia, R. A. Mckay, and C. L. Cioffi, "Inhibition of C-Jun N-terminal kinase 1, but not c-Jun N-terminal kinase 2, suppresses apoptosis induced by ischemia/reoxygenation in rat cardiac myocytes," Molecular Pharmacology, vol. 59, no. 4, pp. 867-874, 2001.
75. C. Ferrandi, R. Ballerio, P. Gaillard et al., "Inhibition of c-Jun Nterminal kinase decreases cardiomyocyte apoptosis and infarct size aftermyocardial ischemia and reperfusion in anaesthetized rats," British Journal of Pharmacology, vol. 142, no. 6, pp. 953-960, 2004.
76. H. Aoki, P. M. Kang, J. Hampe et al., "Direct activation of mitochondrial apoptosis machinery by c-Jun n-terminal kinase in adult cardiac myocytes," Journal of Biological Chemistry, vol. 277, no. 12, pp. 10244-10250, 2002.
77. R. A. Kaiser, Q. Liang, O. Bueno et al., "Genetic inhibition or activation of JNK1/2 protects the myocardium from ischemiareperfusion-induced cell death in vivo," Journal of Biological Chemistry, vol. 280, no. 38, pp. 32602-32608, 2005.
78. D. Qi, X. Hu, X. Wu et al., "Cardiac macrophage migration inhibitory factor inhibits JNK pathway activation and injury during ischemia/reperfusion," The Journal of Clinical Investigation, vol. 119, no. 12, pp. 3807-3816, 2009.
79. Y. Pan, Y. Wang, Y. Zhao et al., "Inhibition of JNK phosphorylation by a novel curcumin analog prevents high glucoseinduced inflammation and apoptosis in cardiomyocytes and the development of diabetic cardiomyopathy," Diabetes, vol. 63, no. 10, pp. 3497-3511, 2014.
80. P. Andreka, J. Zang, C. Dougherty, T. I. Slepak, K. A. Webster, and N. H. Bishopric, "Cytoprotection by Jun kinase during nitric oxide-induced cardiac myocyte apoptosis," Circulation Research, vol. 88, no. 3, pp. 305-312, 2001.
81. C. J. Dougherty, L. A. Kubasiak, H. Prentice, P. Andreka, N. H. Bishopric, and K. A. Webster, "Activation of c-Jun N-terminal kinase promotes survival of cardiac myocytes after oxidative stress," Biochemical Journal, vol. 362, no. 3, pp. 561-571, 2002.
82. A.-M. Engelbrecht, C. Niesler, C. Page, and A. Lochner, "p38 and JNK have distinct regulatory functions on the development of apoptosis during simulated ischaemia and reperfusion in neonatal cardiomyocytes," Basic Research in Cardiology, vol. 99, no. 5, pp. 338-350, 2004.
83. Z. Shao, K. Bhattacharya, E. Hsich et al., "c-Jun N-terminal kinasesmediate reactivation of Akt and cardiomyocyte survival after hypoxic injury in vitro and in vivo," Circulation Research, vol. 98, no. 1, pp. 111-118, 2006.
84. T. H. Tran, P. Andreka, C. O. Rodrigues, K. A. Webster, and N. H. Bishopric, "Jun kinase delays caspase-9 activation by interaction with the apoptosome," Journal of Biological Chemistry, vol. 282, no. 28, pp. 20340-20350, 2007.
85. X. L. Ma, S. Kumar, F. Gao et al., "Inhibition of p38 mitogenactivated protein kinase decreases cardiomyocyte apoptosis and improves cardiac function after myocardial ischemia and reperfusion," Circulation, vol. 99, no. 13, pp. 1685-1691, 1999.
86. Y. J. Kang, Z.-X. Zhou, G.-W. Wang, A. Buridi, and J. B. Klein, "Suppression by metallothionein of doxorubicin-induced cardiomyocyte apoptosis through inhibition of p38 mitogenactivated protein kinases," The Journal of Biological Chemistry, vol. 275, no. 18, pp. 13690-13698, 2000.
87. K. Otsu, N. Yamashita, K. Nishida et al., "Disruption of a single copy of the p38α MAP kinase gene leads to cardioprotection against ischemia-reperfusion," Biochemical and Biophysical Research Communications, vol. 302, no. 1, pp. 56-60, 2003.
88. R. A. Kaiser, O. F. Bueno, D. J. Lips et al., "Targeted inhibition of p38 mitogen-activated protein kinase antagonizes cardiac injury and cell death following ischemia-reperfusion in vivo," Journal of Biological Chemistry, vol. 279, no. 15, pp. 15524-15530, 2004.
89. J. Ren, S. Zhang, A. Kovacs, Y. Wang, and A. J. Muslin, "Role of p38α MAPK in cardiac apoptosis and remodeling after myocardial infarction," Journal of Molecular and Cellular Cardiology, vol. 38, no. 4, pp. 617-623, 2005.
90. S. Sanada, M. Kitakaze, P. J. Papst et al., "Role of phasic dynamism of p38 mitogen-activated protein kinase activation in ischemic preconditioning of the canine heart," Circulation Research, vol. 88, no. 2, pp. 175-180, 2001.
91. A. T. Saurin, J. L. Martin, R. J. Heads et al., "The role of differential activation of p38-mitogen-activated protein kinase in preconditioned ventricularmyocytes," FASEB Journal, vol. 14, no. 14, pp. 2237-2246, 2000.
92. J.-H. Hu, T. Chen, Z.-H. Zhuang et al., "Feedback control of MKP-1 expression by p38," Cellular Signalling, vol. 19, no. 2, pp. 393-400, 2007.
93. H.-Y. Sun, N.-P. Wang, M. Halkos et al., "Postconditioning attenuates cardiomyocyte apoptosis via inhibition of JNK and p38 mitogen-activated protein kinase signaling pathways," Apoptosis, vol. 11, no. 9, pp. 1583-1593, 2006.
94. K. K. Jin, A. Pedram, M. Razandi, and E. R. Levin, "Estrogen prevents cardiomyocyte apoptosis through inhibition of reactive oxygen species and differential regulation of p38 kinase isoforms," Journal of Biological Chemistry, vol. 281, no. 10, pp. 6760-6767, 2006.
95. C. Li, T. Wang, C. Zhang, J. Xuan, C. Su, and Y. Wang, "Quercetin attenuates cardiomyocyte apoptosis via inhibition of JNK and p38 mitogen-activated protein kinase signaling pathways," Gene, vol. 577, no. 2, pp. 275-280, 2016.
96. S. Israeli-Rosenberg, A. M. Manso, H. Okada, and R. S. Ross, "Integrins and integrin-associated proteins in the cardiac myocyte," Circulation Research, vol. 114, no. 3, pp. 572-586, 2014.
97. R. Fassler and M. Meyer, "Consequences of lack of β1 integrin gene expression in mice," Genes and Development, vol. 9, no. 15, pp. 1896-1908, 1995.
98. L. E. Stephens, A. E. Sutherland, I. V. Klimanskaya et al., "Deletion of beta 1 integrins in mice results in inner cell mass failure and peri-implantation lethality," Genes and Development, vol. 9, no. 15, pp. 1883-1895, 1995.
99. M. Ieda, T. Tsuchihashi, K. N. Ivey et al., "Cardiac fibroblasts regulate myocardial proliferation through β1 integrin signaling," Developmental Cell, vol. 16, no. 2, pp. 233-244, 2009.
100. P. Krishnamurthy, V. Subramanian, M. Singh, and K. Singh, "Deficiency of β1 integrins results in increased myocardial dysfunction after myocardial infarction," Heart, vol. 92, no. 9, pp. 1309-1315, 2006.
101. P. Krishnamurthy, V. Subramanian, M. Singh, and K. Singh, "β1 integrins modulate β-adrenergic receptor-stimulated cardiac myocyte apoptosis and myocardial remodeling," Hypertension, vol. 49, no. 4, pp. 865-872, 2007.
102. R. Li, Y. Wu, A.M. Mansoet al., "β1 integrin gene excision in the adult murine cardiac myocyte causes defective mechanical and signaling responses," American Journal of Pathology, vol. 180, no. 3, pp. 952-962, 2012.
103. S.-Y. Shai, A. E. Harpf, C. J. Babbitt et al., "Cardiac myocytespecific excision of the β1 integrin gene results in myocardial fibrosis and cardiac failure," Circulation Research, vol. 90, no. 4, pp. 458-464, 2002.
104. H. Okada, N. C. Lai, Y. Kawaraguchi et al., "Integrins protect cardiomyocytes from ischemia/reperfusion injury," Journal of Clinical Investigation, vol. 123, no. 10, pp. 4294-4308, 2013.
105. Z. S. Hakim, L. A. DiMichele, M. Rojas, D. Meredith, C. P. Mack, and J. M. Taylor, "FAK regulates cardiomyocyte survival following ischemia/reperfusion," Journal of Molecular and Cellular Cardiology, vol. 46, no. 2, pp. 241-248, 2009.
106. Z. Cheng, L. A. DiMichele, Z. S. Hakim, M. Rojas, C. P. Mack, and J. M. Taylor, "Targeted focal adhesion kinase activation in cardiomyocytes protects the heart from ischemia/reperfusion injury," Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 32, no. 4, pp. 924-933, 2012.
107. Cip1," Journal of Molecular and Cellular Cardiology, vol. 67, pp. 1-11, 2014.
108. S. Gilles, S. Zahler, U. Welsch, C. P. Sommerhoff, and B. F. Becker, "Release of TNF-α during myocardial reperfusion depends on oxidative stress and is prevented by mast cell stabilizers," Cardiovascular Research, vol. 60, no. 3, pp. 608-616, 2003.
109. A. Diwan, Z. Dibbs, S. Nemoto et al., "Targeted overexpression of noncleavable and secreted forms of tumor necrosis factor provokes disparate cardiac phenotypes," Circulation, vol. 109, no. 2, pp. 262-268, 2004.
110. S. B. Haudek, G. E. Taffet, M. D. Schneider, and D. L. Mann, "TNF provokes cardiomyocyte apoptosis and cardiac remodeling through activation of multiple cell death pathways," The Journal of Clinical Investigation, vol. 117, no. 9, pp. 2692-2701, 2007.
111. P. Panagopoulou, C. H. Davos, D. J. Milner et al., "Desmin mediates TNF-α-induced aggregate formation and intercalated disk reorganization in heart failure," Journal of Cell Biology, vol. 181, no. 5, pp. 761-775, 2008.
112. 2+ ATPase expression and leads to left ventricular diastolic dysfunction through binding of NF-κB to promoter response element," Cardiovascular Research, vol. 105, no. 3, pp. 318-329, 2015.
113. N. Maekawa, H. Wada, T. Kanda et al., "Improved myocardial ischemia/reperfusion injury in mice lacking tumor necrosis factor-α," Journal of the American College of Cardiology, vol. 39, no. 7, pp. 1229-1235, 2002.
114. M. Sun, F. Dawood, W.-H. Wen et al., "Excessive tumor necrosis factor activation after infarction contributes to susceptibility of myocardial rupture and left ventricular dysfunction," Circulation, vol. 110, no. 20, pp. 3221-3228, 2004.
115. M. P. Flaherty, Y. Guo, S. Tiwari et al., "The role of TNF-α receptors p55 and p75 in acutemyocardial ischemia/reperfusion injury and late preconditioning," Journal of Molecular and Cellular Cardiology, vol. 45, no. 6, pp. 735-741, 2008.
116. Y. Monden, T. Kubota, T. Inoue et al., "Tumor necrosis factor-α is toxic via receptor 1 and protective via receptor 2 in a murine model of myocardial infarction," American Journal of Physiology-Heart and Circulatory Physiology, vol. 293, no. 1, pp. H743-H753, 2007.
117. T. Hamid, Y. Gu, R. V. Ortines et al., "Divergent tumor necrosis factor receptor-related remodeling responses in heart failure: role of nuclear factor-κB and inflammatory activation," Circulation, vol. 119, no. 10, pp. 1386-1397, 2009.
118. K. M. Kurrelmeyer, L. H. Michael, G. Baumgarten et al., "Endogenous tumor necrosis factor protects the adult cardiac myocyte against ischemic-induced apoptosis in amurinemodel of acute myocardial infarction," Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 10, pp. 5456-5461, 2000.
119. T. Kubota, M. Miyagishima, C. S. Frye et al., "Overexpression of tumor necrosis factor-α activates both anti- and pro-apoptotic pathways in themyocardium," Journal of Molecular and Cellular Cardiology, vol. 33, no. 7, pp. 1331-1344, 2001.
120. J. S. Burchfield, J.-W. Dong, Y. Sakata et al., "The cytoprotective effects of tumor necrosis factor are conveyed through tumor necrosis factor receptor-associated factor 2 in the heart," Circulation: Heart Failure, vol. 3, no. 1, pp. 157-164, 2010.
121. A. Misra, S. B. Haudek, P. Knuefermann et al., "Nuclear factor-κB protects the adult cardiacmyocyte against ischemia-induced apoptosis in a murine model of acute myocardial infarction," Circulation, vol. 108, no. 25, pp. 3075-3078, 2003.
122. J. Shaw, T. Zhang, M. Rzeszutek et al., "Transcriptional silencing of the death gene BNIP3 by cooperative action of NF-κB and histone deacetylase 1 in ventricular myocytes," Circulation Research, vol. 99, no. 12, pp. 1347-1354, 2006.
123. S. Papathanasiou, S. Rickelt, M. E. Soriano et al., "Tumor necrosis factor-α confers cardioprotection through ectopic expression of keratins K8 and K18," Nature Medicine, vol. 21, no. 9, pp. 1076-1084, 2015.
124. P. Kratsios, M. Huth, L. Temmerman et al., "Antioxidant amelioration of dilated cardiomyopathy caused by conditional deletion of NEMO/IKKγ in cardiomyocytes," Circulation Research, vol. 106, no. 1, pp. 133-144, 2010.
125. H. J. Maier, T. G. Schips, A. Wietelmann et al., "Cardiomyocyte specific IκB kinase (IKK)/NF-κB activation induces reversible inflammatory cardiomyopathy and heart failure," Proceedings of the National Academy of Sciences of the United States of America, vol. 109, no. 29, pp. 11794-11799, 2012.
126. T. Hamid, S. Z. Guo, J. R. Kingery, X. Xiang, B. Dawn, and S. D. Prabhu, "Cardiomyocyte NF-κB p65 promotes adverse remodelling, apoptosis, and endoplasmic reticulum stress in heart failure," Cardiovascular Research, vol. 89, no. 1, pp. 129-138, 2011.
127. X. Q. Zhang, R. Tang, L. Li et al., "Cardiomyocyte-specific p65 NF-κB deletion protects the injured heart by preservation of calcium handling," American Journal of Physiology-Heart and Circulatory Physiology, vol. 305, no. 7, pp. H1089-H1097, 2013.
128. M. Brown, M. McGuinness, T. Wright et al., "Cardiac-specific blockade of NF-κB in cardiac pathophysiology: differences between acute and chronic stimuli in vivo," American Journal of Physiology-Heart and Circulatory Physiology, vol. 289, no. 1, pp. H466-H476, 2005.
129. S. Kawano, T. Kubota, Y. Monden et al., "Blockade of NF-κB improves cardiac function and survival aftermyocardial infarction," American Journal of Physiology-Heart and Circulatory Physiology, vol. 291, no. 3, pp. H1337-H1344, 2006.
130. S. Frantz, K. Hu, B. Bayer et al., "Absence of NF-κB subunit p50 improves heart failure after myocardial infarction," The FASEB journal, vol. 20, no. 11, pp. 1918-1920, 2006.
131. L. Timmers, J. K. Van Keulen, I. E. Hoefer et al., "Targeted deletion of nuclear factor κB p50 enhances cardiac remodeling and dysfunction following myocardial infarction," Circulation Research, vol. 104, no. 5, pp. 699-706, 2009.
132. J. W. Gordon, J. A. Shaw, and L. A. Kirshenbaum, "Multiple facets of NF-κB in the heart: to be or not to NF-κB," Circulation Research, vol. 108, no. 9, pp. 1122-1132, 2011.
133. Y. Wang, E. Gao, W. B. Lau et al., "G-protein-coupled receptor kinase 2-mediated desensitization of adiponectin receptor 1 in failing heart," Circulation, vol. 131, no. 16, pp. 1392-1404, 2015.
134. M. Chen, P. Y. Sato, J. K. Chuprun et al., "Prodeath signaling of G protein-coupled receptor kinase 2 in cardiac myocytes after ischemic stress occurs via extracellular signal-regulated kinasedependent heat shock protein 90-mediated mitochondrial targeting," Circulation Research, vol. 112, no. 8, pp. 1121-1134, 2013.
135. Q. Fan, M. Chen, L. Zuo et al., "Myocardial ablation of G protein-coupled receptor kinase 2 (GRK2) decreases ischemia/reperfusion injury through an anti-intrinsic apoptotic pathway," PLoS ONE, vol. 8, no. 6, Article ID e66234, 2013.
136. N. C. Salazar, J. Chen, and H. A. Rockman, "Cardiac GPCRs: GPCR signaling in healthy and failing hearts," Biochimica et Biophysica Acta-Biomembranes, vol. 1768, no. 4, pp. 1006-1018, 2007.
137. T. D. O'Connell, B. C. Jensen, A. J. Baker, and P. C. Simpson, "Cardiac alpha1-adrenergic receptors: novel aspects of expression, signaling mechanisms, physiologic function, and clinical importance," Pharmacological Reviews, vol. 66, no. 1, pp. 308-333, 2014.
138. 2-adrenergic receptors on cardiac myocyte apoptosis: role of a pertussis toxin-sensitive Gprotein," Circulation, vol. 100, no. 22, pp. 2210-2212, 1999.
139. M. Zaugg, W. Xu, E. Lucchinetti, S. A. Shafiq, N. Z. Jamali, and M. A. Q. Siddiqui, "β-Adrenergic receptor subtypes differentially affect apoptosis in adult rat ventricular myocytes," Circulation, vol. 102, no. 3, pp. 344-350, 2000.
140. S.-Y. Shin, T. Kim, H.-S. Lee et al., "The switching role of β-adrenergic receptor signalling in cell survival or death decision of cardiomyocytes," Nature Communications, vol. 5, article 5777, 2014.
141. S. Saito, Y. Hiroi, Y. Zou et al., "β-adrenergic pathway induces apoptosis through calcineurin activation in cardiac myocytes," Journal of Biological Chemistry, vol. 275, no. 44, pp. 34528-34533, 2000.
142. 2+/calmodulin kinase II," The Journal of Clinical Investigation, vol. 111, no. 5, pp. 617-625, 2003.
143. Y.-C. Fu, C.-S. Chi, S.-C. Yin, B. Hwang, Y.-T. Chiu, and S.-L. Hsu, "Norepinephrine induces apoptosis in neonatal rat cardiomyocytes through a reactive oxygen species-TNFα-caspase signaling pathway," Cardiovascular Research, vol. 62, no. 3, pp. 558-567, 2004.
144. 2-adrenergic signaling in adult mouse cardiac myocytes," Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 4, pp. 1607-1612, 2001.
145. W. Zhang, N. Yano, M. Deng, Q. Mao, S. K. Shaw, and Y.-T. Tseng, "β-Adrenergic receptor-PI3K signaling crosstalk in mouse heart: elucidation of immediate downstream signaling cascades," PLoS ONE, vol. 6, no. 10, Article IDe26581, 2011.
146. A. Chesley, M. S. Lundberg, T. Asai et al., "The β2-adrenergic receptor delivers an antiapoptotic signal to cardiac myocytes through G(i)-dependent coupling to phosphatidylinositol 3′-kinase," Circulation Research, vol. 87, no. 12, pp. 1172-1179, 2000.
147. Y.-J. Geng, Y. Ishikawa, D. E. Vatner et al., "Apoptosis of cardiac myocytes in Gsα transgenic mice," Circulation Research, vol. 84, no. 1, pp. 34-42, 1999.
148. B. R. DeGeorge Jr., E. Gao, M. Boucher et al., "Targeted inhibition of cardiomyocyte Gi signaling enhances susceptibility to apoptotic cell death in response to ischemic stress," Circulation, vol. 117, no. 11, pp. 1378-1387, 2008.
149. i or Gβγ in adult mouse cardiomyocytes," Journal of Biological Chemistry, vol. 275, pp. 40635-40640, 2000.
150. J. G. Burniston, L.-B. Tan, and D. F. Goldspink, "β2-adrenergic receptor stimulation in vivo induces apoptosis in the rat heart and soleus muscle," Journal of Applied Physiology, vol. 98, no. 4, pp. 1379-1386, 2005.
151. 1-adrenergic cardiomyopathy by reducing myocyte necrosis and non-myocyte apoptosis rather thanmyocyte apoptosis," Basic Research in Cardiology, vol. 110, 2015.
152. E. Iwai-Kanai, K. Hasegawa, M. Araki, T. Kakita, T. Morimoto, and S. Sasayama, "α- and β-adrenergic pathways differentially regulate cell type-specific apoptosis in rat cardiac myocytes," Circulation, vol. 100, no. 3, pp. 305-311, 1999.
153. H. Zhu, S. McElwee-Witmer, M. Perrone, K. L. Clark, and A. Zilberstein, "Phenylephrine protects neonatal rat cardiomyocytes from hypoxia and serum deprivation-induced apoptosis," Cell Death & Differentiation, vol. 7, no. 9, pp. 773-784, 2000.
154. A. Aries, P. Paradis, C. Lefebvre, R. J. Schwartz, and M. Nemer, "Essential role of GATA-4 in cell survival and drug-induced cardiotoxicity," Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 18, pp. 6975-6980, 2004.
155. 1-Adrenergic receptors prevent a maladaptive cardiac response to pressure overload," The Journal of Clinical Investigation, vol. 116, no. 4, pp. 1005-1015, 2006.
156. H. Chaulet, F. Lin, J. Guo et al., "Sustained augmentation of cardiac α1A-adrenergic drive results in pathological remodeling with contractile dysfunction, progressive fibrosis and reactivation of matricellular protein genes," Journal of Molecular and Cellular Cardiology, vol. 40, no. 4, pp. 540-552, 2006.
157. A. L. Howes, S. Miyamoto, J. W. Adams, E. A. Woodcock, and J. H. Brown, "Gαq expression activates EGFR and induces Akt mediated cardiomyocyte survival: dissociation from Gαqmediated hypertrophy," Journal of Molecular and Cellular Cardiology, vol. 40, no. 5, pp. 597-604, 2006.
158. A. L. Howes, J. F. Arthur, T. Zhang et al., "Akt-mediated cardiomyocyte survival pathways are compromised by Gαqinduced phosphoinositide 4,5-bisphosphate depletion," Journal of Biological Chemistry, vol. 278, no. 41, pp. 40343-40351, 2003.
159. J. Shi, Y.-W. Zhang, Y. Yang, L. Zhang, and L. Wei, "ROCK1 plays an essential role in the transition from cardiac hypertrophy to failure in mice," Journal of Molecular and Cellular Cardiology, vol. 49, no. 5, pp. 819-828, 2010.
160. M. Araki, K. Hasegawa, E. Iwai-Kanai et al., "Endothelin-1 as a protective factor against beta-adrenergic agonist-induced apoptosis in cardiac myocytes," Journal of the American College of Cardiology, vol. 36, no. 4, pp. 1411-1418, 2000.
161. A. Ren, X. Yan, H. Luet al., "Antagonismof endothelin-1 inhibits hypoxia-induced apoptosis in cardiomyocytes," Canadian Journal of Physiology and Pharmacology, vol. 86, no. 8, pp. 536-540, 2008.
162. E. Øie, O. P. F. Clausen, A. Yndestad, H. K. Grøgaard, and H. Attramadal, "Endothelin receptor antagonism attenuates cardiomyocyte apoptosis after induction of ischemia in rats," Scandinavian Cardiovascular Journal, vol. 36, no. 2, pp. 108-116, 2002.
163. S. Tamareille, M. Terwelp, J. Amirian et al., "Endothelin-1 release during the early phase of reperfusion is a mediator of myocardial reperfusion injury," Cardiology, vol. 125, no. 4, pp. 242-249, 2013.
164. S. Bien, A. Riad, C. A. Ritter et al., "The endothelin receptor blocker bosentan inhibits doxorubicin-induced cardiomyopathy," Cancer Research, vol. 67, no. 21, pp. 10428-10435, 2007.
165. X.-S. Zhao, W. Pan, R. Bekeredjian, and R.V. Shohet, "Endogenous endothelin-1 is required for cardiomyocyte survival in vivo," Circulation, vol. 114, no. 8, pp. 830-837, 2006.
166. A receptor mitigates low ambient temperature-induced cardiac hypertrophy and contractile dysfunction," Journal of Molecular Cell Biology, vol. 4, no. 2, pp. 97-107, 2012.
167. I. Goldenberg, E. Grossman, K. A. Jacobson, V. Shneyvays, and A. Shainberg, "Angiotensin II-induced apoptosis in rat cardiomyocyte culture: a possible role of AT1 and AT2 receptors," Journal of Hypertension, vol. 19, no. 9, pp. 1681-1689, 2001.
168. 1 receptor blockade on cardiac apoptosis in angiotensin IIinduced hypertension," American Journal of Physiology-Heart and Circulatory Physiology, vol. 282, no. 5, pp. H1635-H1641, 2002.
169. H. Sugino, R. Ozono, S. Kurisu et al., "Apoptosis is not increased in myocardium overexpressing type 2 angiotensin II receptor in transgenic mice," Hypertension, vol. 37, no. 6, pp. 1394-1398, 2001.
170. J. F. X. Ainscough, M. J. Drinkhill, A. Sedo et al., "Angiotensin II type-1 receptor activation in the adult heart causes blood pressure-independent hypertrophy and cardiac dysfunction," Cardiovascular Research, vol. 81, no. 3, pp. 592-600, 2009.
171. M. Nishida, S. Tanabe, Y. Maruyama et al., "Gα12/13- and reactive oxygen species-dependent activation of c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinase by angiotensin receptor stimulation in rat neonatal cardiomyocytes," The Journal of Biological Chemistry, vol. 280, no. 18, pp. 18434-18441, 2005.
172. C.-Y. Huang, W.-W. Kuo, Y.-L. Yeh et al., "ANG II promotes IGF-IIR expression and cardiomyocyte apoptosis by inhibiting HSF1 via JNKactivation and SIRT1 degradation," Cell Death and Differentiation, vol. 21, no. 8, pp. 1262-1274, 2014.
173. I. Goldenberg, A. Shainberg, K. A. Jacobson, V. Shneyvays, and E. Grossman, "Adenosine protects againts angiotensin IIinduced apoptosis in rat cardiocyte cultures," Molecular and Cellular Biochemistry, vol. 252, no. 1-2, pp. 133-139, 2003.
174. 3 receptors in newborn rat cardiomyocytes," Journal of Molecular and Cellular Cardiology, vol. 37, no. 5, pp. 989-999, 2004.
175. R. Germack and J. M. Dickenson, "Adenosine triggers preconditioning through MEK/ERK1/2 signalling pathway during hypoxia/reoxygenation in neonatal rat cardiomyocytes," Journal of Molecular and Cellular Cardiology, vol. 39, no. 3, pp. 429-442, 2005.
176. Q. Zhou, L. Li, B. Zhao, and K.-L. Guan, "The hippo pathway in heart development, regeneration, and diseases," Circulation Research, vol. 116, no. 8, pp. 1431-1447, 2015.
177. S. Yamamoto, G. Yang, D. Zablocki et al., "Activation of Mst1 causes dilated cardiomyopathy by stimulating apoptosis without compensatory ventricular myocyte hypertrophy," The Journal of Clinical Investigation, vol. 111, no. 10, pp. 1463-1474, 2003.
178. M. Odashima, S. Usui, H. Takagi et al., "Inhibition of endogenous Mst1 prevents apoptosis and cardiac dysfunction without affecting cardiac hypertrophy after myocardial infarction," Circulation Research, vol. 100, no. 9, pp. 1344-1352, 2007.
179. Y. Maejima, S. Kyoi, P. Zhai et al., "Mst1 inhibits autophagy by promoting the interaction between beclin1 and Bcl-2," Nature Medicine, vol. 19, no. 11, pp. 1478-1488, 2013.
180. D. P. Del Re, T. Matsuda, P. Zhai et al., "Mst1 promotes cardiac myocyte apoptosis through phosphorylation and inhibition of Bcl-xL," Molecular Cell, vol. 54, no. 4, pp. 639-650, 2014.
181. M. Nakamura, P. Zhai, D. P. Del Re, Y. Maejima, and J. Sadoshima, "Mst1-mediated phosphorylation of Bcl-xL is required for myocardial reperfusion injury," JCI Insight, vol. 1, no. 5, 2016.
182. S. Oh, D. Lee, T. Kim et al., "Crucial role for Mst1 and Mst2 kinases in early embryonic development of the mouse," Molecular and Cellular Biology, vol. 29, no. 23, pp. 6309-6320, 2009.
183. D. P. Del Re, T. Matsuda, P. Zhai et al., "Proapoptotic Rassf1A/Mst1 signaling in cardiac fibroblasts is protective against pressure overload in mice," The Journal of Clinical Investigation, vol. 120, no. 10, pp. 3555-3567, 2010.
184. T. Matsuda, P. Zhai, S. Sciarretta et al., "NF2 activates hippo signaling and promotes ischemia/reperfusion injury in the Heart-Novelty and significance," Circulation Research, vol. 119, no. 5, pp. 596-606, 2016.
185. S. Sciarretta, P. Zhai, Y. Maejima et al., "mTORC2 regulates cardiac response to stress by inhibiting MST1," Cell Reports, vol. 11, no. 1, pp. 125-136, 2015.
186. Y. Matsui, N. Nakano, D. Shao et al., "Lats2 is a negative regulator ofmyocyte size in the heart," Circulation Research, vol. 103, no. 11, pp. 1309-1318, 2008.
187. D. P. Del Re, Y. Yang, N. Nakano et al., "Yes-associated protein isoform 1 (Yap1) promotes cardiomyocyte survival and growth to protect against myocardial ischemic injury," Journal of Biological Chemistry, vol. 288, no. 6, pp. 3977-3988, 2013.
188. M. Xin, Y. Kim, L. B. Sutherland et al., "Hippo pathway effector Yap promotes cardiac regeneration," Proceedings of the National Academy of Sciences of the United States of America, vol. 110, no. 34, pp. 13839-13844, 2013.
189. Z. Lin, A. von Gise, P. Zhou et al., "Cardiac-specific YAP activation improves cardiac function and survival in an experimental murine MI model," Circulation Research, vol. 115, no. 3, pp. 354-363, 2014.
190. V. P. Sah, S. Minamisawa, S. P. Tam et al., "Cardiac-specific overexpression of RhoA results in sinus and atrioventricular nodal dysfunction and contractile failure," The Journal of Clinical Investigation, vol. 103, no. 12, pp. 1627-1634, 1999.
191. D. P. Del Re, S. Miyamoto, and J. H. Brown, "RhoA/Rho kinase up-regulate Bax to activate a mitochondrial death pathway and induce cardiomyocyte apoptosis," Journal of Biological Chemistry, vol. 282, no. 11, pp. 8069-8078, 2007.
192. D. P. Del Re, S. Miyamoto, and J. H. Brown, "Focal adhesion kinase as a RhoA-activable signaling scaffold mediating akt activation and cardiomyocyte protection," Journal of Biological Chemistry, vol. 283, no. 51, pp. 35622-35629, 2008.
193. S. Y. Xiang, D. Vanhoutte, D. P. Del Re et al., "RhoA protects the mouse heart against ischemia/reperfusion injury," Journal of Clinical Investigation, vol. 121, no. 8, pp. 3269-3276, 2011.
194. P. A. J. Krijnen, J. A. Sipkens, J. W. Molling et al., "Inhibition of Rho-ROCK signaling induces apoptotic and non-apoptotic PS exposure in cardiomyocytes via inhibition of flippase," Journal of Molecular and Cellular Cardiology, vol. 49, no. 5, pp. 781-790, 2010.
195. X. Yang, Q. Li, X. Lin et al., "Mechanism of fibrotic cardiomyopathy in mice expressing truncated Rho-associated coiled-coil protein kinase 1," The FASEB Journal, vol. 26, no. 5, pp. 2105-2116, 2012.
196. J. Shi, X. Wu, M. Surma et al., "Distinct roles for ROCK1 and ROCK2 in the regulation of cell detachment," Cell Death and Disease, vol. 4, no. 2, article no. e483, 2013.
197. R. Okamoto, Y. Li, K. Noma et al., "FHL2 prevents cardiac hypertrophy in mice with cardiac-specific deletion of ROCK2," FASEB Journal, vol. 27, no. 4, pp. 1439-1449, 2013.
198. E. Shen, Y. Li, Y. Li et al., "Rac1 is required for cardiomyocyte apoptosis during hyperglycemia," Diabetes, vol. 58, no. 10, pp. 2386-2395, 2009.
199. M. A. Sussman, S. Welch, A. Walker et al., "Altered focal adhesion regulation correlates with cardiomyopathy in mice expressing constitutively active rac1," The Journal of Clinical Investigation, vol. 105, no. 7, pp. 875-886, 2000.
200. M. T. Elnakish, M. D. H. Hassona, M. A. Alhaj et al., "Racinduced left ventricular dilation in thyroxin-treated zmracd transgenic mice: role of cardiomyocyte apoptosis and myocardial fibrosis," PLoS ONE, vol. 7, no. 8, Article ID e42500, 2012.
201. M. Maillet, J. M. Lynch, B. Sanna, A. J. York, Y. Zheng, and J. D. Molkentin, "Cdc42 is an antihypertrophic molecular switch in the mouse heart," The Journal of Clinical Investigation, vol. 119, no. 10, pp. 3079-3088, 2009.
202. L. R. Pearce, D. Komander, and D. R. Alessi, "The nuts and bolts of AGC protein kinases," Nature Reviews Molecular Cell Biology, vol. 11, no. 1, pp. 9-22, 2010.
203. J. C. Braz, O. F. Bueno, L. J. De Windt, and J. D. Molkentin, "PKCα regulates the hypertrophic growth of cardiomyocytes through extracellular signal-regulated kinase1/2 (ERK1/2)," Journal of Cell Biology, vol. 156, no. 5, pp. 905-919, 2002.
204. Q. Liu, X. Chen, S. M. Macdonnell et al., "Protein kinase Cα, but Not PKCβ or PKCγ, regulates contractility and heart failure susceptibility: implications for ruboxistaurin as a novel therapeutic approach," Circulation Research, vol. 105, no. 2, pp. 194-200, 2009.
205. M. Song, S. J. Matkovich, Y. Zhang, D. J. Hammer, and G. W. Dorn II, "Combined cardiomyocyte PKCδ and PKC∈ gene deletion uncovers their central role in restraining developmental and reactive heart growth," Science Signaling, vol. 8, no. 373, article ra39, 2015.
206. ∈-interacting with calcium-sensing receptors to inhibit endo(sarco)plasmic reticulum-mitochondria crosstalk," Molecular and Cellular Biochemistry, vol. 341, no. 1-2, pp. 195-206, 2010.
207. +(ATP) channel subunit (Kir6.1) in cardiomyocytemitochondria: implications in cytoprotection against hypoxia induced cell apoptosis," Cellular Signalling, vol. 26, no. 9, pp. 1909-1917, 2014.
208. R. Paoletti, A. Maffei, L. Madaro et al., "Protein kinase Cθ is required for cardiomyocyte survival and cardiac remodeling," Cell Death and Disease, vol. 1, no. 5, article e45, 2010.
209. J. Wang, M. W. Nachtigal, E. Kardami, and P. A. Cattini, "FGF-2 protects cardiomyocytes from doxorubicin damage via protein kinase C-dependent effects on efflux transporters," Cardiovascular Research, vol. 98, no. 1, pp. 56-63, 2013.
210. Y. Wang, J. Zhao, W. Yang et al., "High-dose alcohol induces reactive oxygen species-mediated apoptosis via PKC-β/p66Shc in mouse primary cardiomyocytes," Biochemical and Biophysical Research Communications, vol. 456, no. 2, pp. 656-661, 2015.
211. L. Zhang, D. Huang, D. Shen et al., "Inhibition of protein kinase C βII isoform ameliorates methylglyoxal advanced glycation endproduct-induced cardiomyocyte contractile dysfunction," Life Sciences, vol. 94, no. 1, pp. 83-91, 2014.
212. S. Shoji, D. C. Parmelee, R.D. Wade et al., "Complete amino acid sequence of the catalytic subunit of bovine cardiacmuscle cyclic AMP-dependent protein kinase," Proceedings of the National Academy of Sciences of the United States of America, vol. 78, no. 2, pp. 848-851, 1981.
213. D. R. Knighton, J. H. Zheng, L. F. Ten Eyck et al., "Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase," Science, vol. 253, no. 5018, pp. 407-414, 1991.
214. S. S. Taylor, R. Ilouz, P. Zhang, and A. P. Kornev, "Assembly of allosteric macromolecular switches: lessons from PKA," Nature Reviews Molecular Cell Biology, vol. 13, no. 10, pp. 646-658, 2012.
215. Y. K. Xiang, "Compartmentalization of β-adrenergic signals in cardiomyocytes," Circulation Research, vol. 109, no. 2, pp. 231-244, 2011.
216. A. Perino, A. Ghigo, E. Ferrero et al., "Integrating cardiac PIP3 and cAMP signaling through a PKA anchoring function of p110γ," Molecular Cell, vol. 42, no. 1, pp. 84-95, 2011.
217. L. B. Bockus and K. M. Humphries, "CAMP-dependent protein kinase (PKA) signaling is impaired in the diabetic heart," Journal of Biological Chemistry, vol. 290, no. 49, pp. 29250-29258, 2015.
218. J. Backs, B. C. Worst, L. H. Lehmann et al., "Selective repression of MEF2 activity by PKA-dependent proteolysis of HDAC4," Journal of Cell Biology, vol. 195, no. 3, pp. 403-415, 2011.
219. Y. Y. Lee, D. Moujalled, M. Doerflinger et al., "CREB-binding protein (CBP) regulates β-adrenoceptor (β-AR)-mediated apoptosis," Cell Death and Differentiation, vol. 20, no. 7, pp. 941-952, 2013.
220. N. L. Estrella, A. L. Clark, C. A. Desjardins, S. E. Nocco, and F. J. Naya, "MEF2D deficiency in neonatal cardiomyocytes triggers cell cycle re-entry and programmed cell death in vitro," The Journal of Biological Chemistry, vol. 290, no. 40, pp. 24367-24380, 2015.
221. X. Gao, B. Lin, S. Sadayappan, and T. B. Patel, "Interactions between the regulatory subunit of type I protein kinase a and p90 ribosomal s6 kinase1 regulate cardiomyocyte apoptosiss," Molecular Pharmacology, vol. 85, no. 2, pp. 357-367, 2014.
222. B. Ding, J.-I. Abe, H. Wei et al., "Functional role of phosphodiesterase 3 in cardiomyocyte apoptosis: implication in heart failure," Circulation, vol. 111, no. 19, pp. 2469-2476, 2005.
223. B. Ding, J.-I. Abe, H. Wei et al., "A positive feedback loop of phosphodiesterase 3 (PDE3) and inducible cAMP early repressor (ICER) leads to cardiomyocyte apoptosis," Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 41, pp. 14771-14776, 2005.
224. S. E. Lehnart, X. H. Wehrens, S. Reiken et al., "Phosphodiesterase 4D deficiency in the ryanodine-receptor complex promotes heart failure and arrhythmias," Cell, vol. 123, no. 1, pp. 25-35, 2005.
225. C. K. Pride, L. Mo, K. Quesnelle et al., "Nitrite activates protein kinase A in normoxia to mediate mitochondrial fusion and tolerance to ischaemia/reperfusion," Cardiovascular Research, vol. 101, no. 1, pp. 57-68, 2014.
226. S. Sun, M. Zhang, J. Lin et al., "Lin28a protects against diabetic cardiomyopathy via the PKA/ROCK2 pathway," Biochemical and Biophysical Research Communications, vol. 469, no. 1, pp. 29-36, 2016.
227. P. Ahuja, P. Sdek, and W. R. MacLellan, "Cardiac myocyte cell cycle control in development, disease, and regeneration," Physiological Reviews, vol. 87, no. 2, pp. 521-544, 2007.
228. A. Besson, S. F. Dowdy, and J.M. Roberts, "CDK inhibitors: cell cycle regulators and beyond," Developmental Cell, vol. 14, no. 2, pp. 159-169, 2008.
229. S. Adachi, H. Ito, M. Tamamori-Adachi et al., "Cyclin A/cdk2 activation is involved in hypoxia-induced apoptosis in cardiomyocytes," Circulation Research, vol. 88, no. 4, pp. 408-414, 2001.
230. L. Hauck, G. Hansmann, R. Dietz, and R. VonHarsdorf, "Inhibition of hypoxia-induced apoptosis bymodulation of retinoblastoma protein-dependent signaling in cardiomyocytes," Circulation Research, vol. 91, no. 9, pp. 782-789, 2002.
231. A. M. Narasimha, M. Kaulich, G. S. Shapiro, Y. J. Choi, P. Sicinski, and S. F. Dowdy, "Cyclin D activates the Rb tumor suppressor by mono-phosphorylation," eLife, vol. 2014, no. 3, Article ID e02872, 2014.
232. Y. Maejima, S. Adachi, H. Ito, K. Nobori, M. Tamamori-Adachi, and M. Isobe, "Nitric oxide inhibits ischemia/reperfusioninduced myocardial apoptosis by modulating cyclin Aassociated kinase activity," Cardiovascular Research, vol. 59, no. 2, pp. 308-320, 2003.
233. R. Agah, L. A. Kirshenbaum, M. Abdellatif et al., "Adenoviral delivery of E2F-1 directs cell cycle reentry and p53- independent apoptosis in postmitotic adult myocardium in vivo," Journal of Clinical Investigation, vol. 100, no. 11, pp. 2722-2728, 1997.
234. KIP1 and release of active cyclin-dependent kinases in the presence of insulin-like growth factor I," Circulation Research, vol. 85, no. 2, pp. 128-136, 1999.
235. N. Yurkova, J. Shaw, K. Blackie et al., "The cell cycle factor E2F-1 activates Bnip3 and the intrinsic death pathway in ventricular myocytes," Circulation Research, vol. 102, no. 4, pp. 472-479, 2008.
236. A. Diwan, M. Krenz, F. M. Syed et al., "Inhibition of ischemic cardiomyocyte apoptosis through targeted ablation of Bnip3 restrains postinfarction remodeling in mice," The Journal of Clinical Investigation, vol. 117, no. 10, pp. 2825-2833, 2007.
237. R. Dhingra, V. Margulets, S. R. Chowdhury et al., "Bnip3 mediates doxorubicin-induced cardiac myocyte necrosis and mortality through changes in mitochondrial signaling," Proceedings of the National Academy of Sciences of the United States of America, vol. 111, no. 51, pp. E5537-E5544, 2014.
238. E. Angelis, P. Zhao, R. Zhang, J. I. Goldhaber, and W. R. MacLellan, "The role of E2F-1 and downstream target genes in mediating ischemia/reperfusion injury in vivo," Journal of Molecular and Cellular Cardiology, vol. 51, no. 6, pp. 919-926, 2011.
239. J. Zhang, N. Bahi, A. M. Zubiaga, J. X. Comella, M. Llovera, and D. Sanchis, "Developmental silencing and independency from E2F of apoptotic gene expression in postmitotic tissues," FEBS Letters, vol. 581, no. 30, pp. 5781-5786, 2007.
240. D. Dingar, F. Konecny, J. Zou, X. Sun, and R. von Harsdorf, "Anti-apoptotic function of the E2F transcription factor 4 (E2F4)/p130, a member of retinoblastoma gene family in cardiacmyocytes," Journal of Molecular and Cellular Cardiology, vol. 53, no. 6, pp. 820-828, 2012.
241. J. L. O. Pohjoismäki, S. L. Williams, T. Boettger et al., "Overexpression of Twinkle-helicase protects cardiomyocytes from genotoxic stress caused by reactive oxygen species," Proceedings of the National Academy of Sciences of the United States of America, vol. 110, no. 48, pp. 19408-19413, 2013.
242. F. Konecny, J. Zou, M. Husain, and R. von Harsdorf, "Postmyocardial infarct p27 fusion protein intravenous delivery averts adverse remodelling and improves heart function and survival in rodents," Cardiovascular Research, vol. 94, no. 3, pp. 492-500, 2012.
243. X. Sun, A. Momen, J. Wu et al., "P27 protein protects metabolically stressed cardiomyocytes from apoptosis by promoting autophagy," Journal of Biological Chemistry, vol. 289, no. 24, pp. 16924-16935, 2014.
244. WAF1/Cip1/Sdi1 knockout mice respond to doxorubicin with reduced cardiotoxicity," Toxicology and Applied Pharmacology, vol. 257, no. 1, pp. 102-110, 2011.
245. N. Zhou, Y. Fu, Y. Wang et al., "P27kip1 haplo-insufficiency improves cardiac function in early-stages of myocardial infarction by protecting myocardium and increasing angiogenesis by promoting IKK activation," Scientific Reports, vol. 4, article no. 5978, 2014.
246. Y. Yan, J. Frisén, M.-H. Lee, J. Massagué, and M. Barbacid, "Ablation of the CDK in hibitor p57Kip2 results in increased apoptosis and delayed differentiation during mouse development," Genes and Development, vol. 11, no. 8, pp. 973-983, 1997.
247. S. A. Haley, T. Zhao, L. Zou, J. E. Klysik, J. F. Padbury, and L.K. Kochilas, "Forced expression of the cell cycle inhibitor p57Kip2 in cardiomyocytes attenuates ischemia-reperfusion injury in the mouse heart," BMC Physiology, vol. 8, article 4, 2008.
248. N. A. Gude, G. Emmanuel, W. Wu et al., "Activation of Notchmediated protective signaling in the myocardium," Circulation Research, vol. 102, no. 9, pp. 1025-1035, 2008.
249. P. Kratsios, C. Catela, E. Salimova et al., "Distinct roles for cellautonomous notch signaling in cardiomyocytes of the embryonic and adult heart," Circulation Research, vol. 106, no. 3, pp. 559-572, 2010.
250. X.-L. Zhou, L. Wan, Q.-R. Xu, Y. Zhao, and J.-C. Liu, "Notch signaling activation contributes to cardioprotection provided by ischemic preconditioning and postconditioning," Journal of Translational Medicine, vol. 11, article 251, 2013.
251. B. Yu and B. Song, "Notch 1 signalling inhibits cardiomyocyte apoptosis in ischaemic postconditioning," Heart Lung and Circulation, vol. 23, no. 2, pp. 152-158, 2014.
252. A. Croquelois, A. A. Domenighetti, M. Nemir et al., "Control of the adaptive response of the heart to stress via the Notchl receptor pathway," Journal of Experimental Medicine, vol. 205, no. 13, pp. 3173-3185, 2008.
253. Y. Li, Y. Hiroi, S. Ngoy et al., "Notch1 in bone marrow-derived cellsmediates cardiac repair aftermyocardial infarction," Circulation, vol. 123, no. 8, pp. 866-876, 2011.
254. C. Collesi, L. Zentilin, G. Sinagra, and M. Giacca, "Notch1 signaling stimulates proliferation of immature cardiomyocytes," Journal of Cell Biology, vol. 183, no. 1, pp. 117-128, 2008.
255. W. Ge and J. Ren, "mTOR-STAT3-notch signalling contributes to ALDH2-induced protection against cardiac contractile dysfunction and autophagy under alcoholism," Journal of Cellular and Molecular Medicine, vol. 16, no. 3, pp. 616-626, 2012.
256. M. Zhang, C. Wang, J. Hu et al., "Notch3/Akt signaling contributes to OSM-induced protection against cardiac ischemia/reperfusion injury," Apoptosis, vol. 20, no. 9, pp. 1150-1163, 2015.
257. V. M. Campa, R. Gutiérrez-Lanza, F. Cerignoli et al., "Notch activates cell cycle reentry and progression in quiescent cardiomyocytes," Journal of Cell Biology, vol. 183, no. 1, pp. 129-141, 2008.
258. H. Pei, Q. Yu, Q. Xue et al., "Notch1 cardioprotection inmyocardial ischemia/reperfusion involves reduction of oxidative/nitrative stress," Basic Research in Cardiology, vol. 108, article 373, 2013.
259. M.-Y. Kim, J. Jung, J.-S. Mo et al., "The intracellular domain of Jagged-1 interacts with Notch1 intracellular domain and promotes its degradation through Fbw7 E3 ligase," Experimental Cell Research, vol. 317, no. 17, pp. 2438-2446, 2011.
260. M. Metrich, A. Bezdek Pomey, C. Berthonneche, A. Sarre, M. Nemir, and T. Pedrazzini, "Jagged1 intracellular domainmediated inhibition of Notch1 signalling regulates cardiac homeostasis in the postnatal heart," Cardiovascular Research, vol. 108, no. 1, pp. 74-86, 2015.
261. 2+ in cardiac myocytes," Biophysical Journal, vol. 95, no. 10, pp. 4597-4612, 2008.
262. L. J. De Windt, H. W. Lim, T. Taigen et al., "Calcineurinmediated hypertrophy protects cardiomyocytes from apoptosis in vitro and in vivo: an apoptosis-independent model of dilated heart failure," Circulation Research, vol. 86, no. 3, pp. 255-263, 2000.
263. O. F. Bueno, D. J. Lips, R. A. Kaiser et al., "Calcineurin Aβ gene targeting predisposes the myocardium to acute ischemiainduced apoptosis and dysfunction," Circulation Research, vol. 94, no. 1, pp. 91-99, 2004.
264. J. Heineke, K. C. Wollert, H. Osinska et al., "Calcineurinprotects the heart in amurinemodel of dilated cardiomyopathy," Journal of Molecular and Cellular Cardiology, vol. 48, no. 6, pp. 1080-1087, 2010.
265. T. Kakita, K. Hasegawa, E. Iwai-Kanai et al., "Calcineurin pathway is required for endothelin-1-mediated protection against oxidant stress-induced apoptosis in cardiac myocytes," Circulation Research, vol. 88, no. 12, pp. 1239-1246, 2001.
266. W. T. Pu, Q. Ma, and S. Izumo, "NFAT transcription factors are critical survival factors that inhibit cardiomyocyte apoptosis during phenylephrine stimulation in vitro," Circulation Research, vol. 92, no. 7, pp. 725-731, 2003.
267. N. Bousette, S. Chugh, V. Fong et al., "Constitutively active calcineurin induces cardiac endoplasmic reticulum stress and protects against apoptosis that is mediated by α-crystallin-B," Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 43, pp. 18481-18486, 2010.
268. 2+-induced apoptosis through calcineurin dephosphorylation of BAD," Science, vol. 284, no. 5412, pp. 339-343, 1999.
269. Q. Liu, B. J. Wilkins, Y. J. Lee, H. Ichijo, and J. D. Molkentin, "Direct interaction and reciprocal regulation between ASK1 and calcineurin-NFAT control cardiomyocyte death and growth," Molecular and Cellular Biology, vol. 26, no. 10, pp. 3785-3797, 2006.
270. H. He, X. Liu, L. Lv et al., "Calcineurin suppresses AMPKdependent cytoprotective autophagy in cardiomyocytes under oxidative stress," Cell Death and Disease, vol. 5, no. 1, article no. e997, 2014.
271. G. H. Little, A. Saw, Y. Bai et al., "Critical role of nuclear calcium/calmodulin-dependent protein kinase IIδB in cardiomyocyte survival in cardiomyopathy," The Journal of Biological Chemistry, vol. 284, no. 37, pp. 24857-24868, 2009.
272. W. Zhu, A. Y.-H. Woo, D. Yang, H. Cheng, M. T. Crow, and R.-P. Xiao, "Activation of CaMKIIδC is a common intermediate of diverse death stimuli-induced heart muscle cell apoptosis," The Journal of Biological Chemistry, vol. 282, no. 14, pp. 10833-10839, 2007.
273. 2+/calmodulin-dependent kinase II in the transition frompressure overload-induced cardiac hypertrophy to heart failure in mice," Journal of Clinical Investigation, vol. 119, no. 5, pp. 1230-1240, 2009.
274. S.M. MacDonnell, J. Weisser-Thomas, H. Kubo et al., "CaMKII negatively regulates calcineurin-NFAT signaling in cardiac myocytes," Circulation Research, vol. 105, no. 4, pp. 316-325, 2009.
275. M.M. Kreusser, L. H. Lehmann, S. Keranov et al., "CardiacCaM kinase II genes δ and γ contribute to adverse remodeling but redundantly inhibit calcineurin-induced myocardial hypertrophy," Circulation, vol. 130, no. 15, pp. 1262-1273, 2014.
276. O. M. Koval, X. Guan, Y. Wu et al., "CaV1.2 β-subunit coordinatesCaMKII-triggered cardiomyocyte death and afterdepolarizations," Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 11, pp. 4996-5000, 2010.
277. M.-L. A. Joiner, O. M. Koval, J. Li et al., "CaMKII determines mitochondrial stress responses in heart," Nature, vol. 491, no. 7423, pp. 269-273, 2012.
278. 2+/calmodulindependent protein kinase II δ mediates myocardial ischemia/reperfusion injury through nuclear factor-κb," Circulation Research, vol. 112, no. 6, pp. 935-944, 2013.
279. M. Weinreuter, M. M. Kreusser, J. Beckendorf et al., "CaM Kinase II mediates maladaptive post-infarct remodeling and pro-inflammatory chemoattractant signaling but not acute myocardial ischemia/reperfusion injury," EMBO Molecular Medicine, vol. 6, no. 10, pp. 1231-1245, 2014.
280. M. Vila-Petroff, M. A. Salas, M. Said et al., "CaMKII inhibition protects against necrosis and apoptosis in irreversible ischemiareperfusion injury," Cardiovascular Research, vol. 73, no. 4, pp. 689-698, 2007.
281. T. Zhang, Y. Zhang, M. Cui et al., "CaMKII is a RIP3 substrate mediating ischemia- and oxidative stress-induced myocardial necroptosis," Nature Medicine, vol. 22, no. 2, pp. 175-182, 2016.
282. J. Narula, N. Haider, R. Virmani et al., "Apoptosis inmyocytes in end-stage heart failure," New England Journal of Medicine, vol. 335, no. 16, pp. 1182-1189, 1996.
283. G. Olivetti, R. Abbi, F. Quaini et al., "Apoptosis in the failing human heart," New England Journal of Medicine, vol. 336, no. 16, pp. 1131-1141, 1997.
284. A. Saraste, K. Pulkki, M. Kallajoki et al., "Cardiomyocyte apoptosis and progression of heart failure to transplantation," European Journal of Clinical Investigation, vol. 29, no. 5, pp. 380-386, 1999.
285. J. Narula, P. Pandey, E. Arbustini et al., "Apoptosis in heart failure: release of cytochrome c from mitochondria and activation of caspase-3 in human cardiomyopathy," Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 14, pp. 8144-8149, 1999.
286. C. Twu, N. Q. Liu, W. Popik et al., "Cardiomyocytes undergo apoptosis in human immunodeficiency virus cardiomyopathy through mitochondrion- and death receptor-controlled pathways," Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 22, pp. 14386-14391, 2002.
287. C. Cristóbal, J. Segovia, L. A. Alonso-Pulpón, E. Castedo, J. A. Vargas, and J. C. Martínez, "Apoptosis and acute cellular rejection in human heart transplants," Revista Espanola de Cardiologia, vol. 63, no. 9, pp. 1061-1069, 2010.
288. T. Vahasilta, M. Malmberg, A. Saraste et al., "Cardiomyocyte apoptosis after antegrade and retrograde cardioplegia during aortic valve surgery," Annals of Thoracic Surgery, vol. 92, no. 4, pp. 1351-1357, 2011.
289. D. Wencker, M. Chandra, K. Nguyen et al., "Amechanistic role for cardiac myocyte apoptosis in heart failure," The Journal of Clinical Investigation, vol. 111, no. 10, pp. 1497-1504, 2003.
290. R. Latini, M. Brines, and F. Fiordaliso, "Do non-hemopoietic effects of erythropoietin play a beneficial role in heart failure?" Heart Failure Reviews, vol. 13, no. 4, pp. 415-423, 2008.
291. E. Lipšic, P. van der Meer, A. A. Voors et al., "A single bolus of a long-acting erythropoietin analogue darbepoetin alfa in patients with acute myocardial infarction: a randomized feasibility and safety study," Cardiovascular Drugs and Therapy, vol. 20, no. 2, pp. 135-141, 2006.
292. M. Ferrario, E. Arbustini, M. Massa et al., "High-dose erythropoietin in patients with acute myocardial infarction: a pilot, randomised, placebo-controlled study," International Journal of Cardiology, vol. 147, no. 1, pp. 124-131, 2011.
293. S. S. Najjar, S. V. Rao, C. Melloni et al., "Intravenous erythropoietin in patients with ST-segment elevation myocardial infarction: REVEAL: a randomized controlled trial," JAMA, vol. 305, no. 18, pp. 1863-1872, 2011.
294. A. A. Voors, A. M. S. Belonje, F. Zijlstra et al., "A single dose of erythropoietin in ST-elevation myocardial infarction," European Heart Journal, vol. 31, no. 21, pp. 2593-2600, 2010.
295. M. L. Fokkema, L. Kleijn, P. Van Der Meer et al., "Long term effects of epoetin alfa in patients with ST-elevation myocardial infarction," Cardiovascular Drugs and Therapy, vol. 27, no. 5, pp. 433-439, 2013.
296. P. Van Der Meer and D. J. Van Veldhuisen, "Acute coronary syndromes: the unfulfilled promise of erythropoietin in patients with MI," Nature Reviews Cardiology, vol. 8, no. 8, pp. 425-426, 2011.
297. A. Messori, V. Fadda, D. Maratea, and S. Trippoli, "Erythropoietin in patients with acute myocardial infarction: no proof of effectiveness or proof of no effectiveness?" Clinical Cardiology, vol. 36, no. 10, pp. E39-E40, 2013.
298. M. L. Fokkema, P. van derMeer, S. V. Rao et al., "Safety and clinical outcome of erythropoiesis-stimulating agents in patients with ST-elevation myocardial infarction: a meta-analysis of individual patient data," American Heart Journal, vol. 168, no. 3, pp. 354-362.e2, 2014.
299. F. Xue, X. Yang, B. Zhang et al., "Postconditioning the human heart in percutaneous coronary intervention," Clinical Cardiology, vol. 33, no. 7, pp. 439-444, 2010.
300. F. Thuny, O. Lairez, F. Roubille et al., "Post-conditioning reduces infarct size and edema in patients with ST-segment elevation myocardial infarction," Journal of the American College of Cardiology, vol. 59, no. 24, pp. 2175-2181, 2012.
301. S. Deftereos, G. Giannopoulos, V. Tzalamouras et al., "Renoprotective effect of remote ischemic post-conditioning by intermittent balloon inflations in patients undergoing percutaneous coronary intervention," Journal of the American College of Cardiology, vol. 61, no. 19, pp. 1949-1955, 2013.
302. J.-Y. Hahn, Y. B. Song, E. K. Kim et al., "Ischemic postconditioning during primary percutaneous coronary intervention: the effects of postconditioning on myocardial reperfusion in patients with st-segment elevation myocardial infarction (POST) randomized trial," Circulation, vol. 128, no. 17, pp. 1889-1896, 2013.
303. J.-Y. Hahn, C. W. Yu, H. S. Park et al., "Long-term effects of ischemic postconditioning on clinical outcomes: 1-year followup of the POST randomized trial," American Heart Journal, vol. 169, no. 5, pp. 639-646, 2015.
304. G. Tarantini, E. Favaretto, M. P. Marra et al., "Postconditioning during coronary angioplasty in acutemyocardial infarction: the POST-AMI trial," International Journal of Cardiology, vol. 162, no. 1, pp. 33-38, 2012.