Table of Contents Author Guidelines Submit a Manuscript
Oxidative Medicine and Cellular Longevity
Volume 2017, Article ID 6437467, 12 pages
https://doi.org/10.1155/2017/6437467
Review Article

Insights for Oxidative Stress and mTOR Signaling in Myocardial Ischemia/Reperfusion Injury under Diabetes

1Department of Cardiac Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an 710032, China
2Department of Anesthesiology, Xi’an Children’s Hospital, Xi’an 710003, China

Correspondence should be addressed to Jian Yang; nc.ude.ummf@naijgnay and Lifang Yang; moc.liamtoh@6gnafilgnay

Received 8 September 2016; Revised 1 December 2016; Accepted 4 January 2017; Published 19 February 2017

Academic Editor: Flávio Reis

Copyright © 2017 Dajun Zhao et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. D. Mozaffarian, E. J. Benjamin, A. S. Go et al., “Executive summary: heart disease and stroke statistics-2016 update: a report from the American Heart Association,” Circulation, vol. 133, no. 4, pp. 447–454, 2016. View at Publisher · View at Google Scholar
  2. A. Zoroufian, T. Razmi, M. Taghavi-Shavazi, M. Lotfi-Tokaldany, and A. Jalali, “Evaluation of subclinical left ventricular dysfunction in diabetic patients: longitudinal strain velocities and left ventricular dyssynchrony by two-dimensional speckle tracking echocardiography study,” Echocardiography, vol. 31, no. 4, pp. 456–463, 2014. View at Publisher · View at Google Scholar · View at Scopus
  3. N. Hamdani, A.-S. Hervent, L. Vandekerckhove et al., “Left ventricular diastolic dysfunction and myocardial stiffness in diabetic mice is attenuated by inhibition of dipeptidyl peptidase 4,” Cardiovascular Research, vol. 104, no. 3, pp. 423–431, 2014. View at Publisher · View at Google Scholar · View at Scopus
  4. A. M. Shah, S. H. Shin, M. Takeuchi et al., “Left ventricular systolic and diastolic function, remodelling, and clinical outcomes among patients with diabetes following myocardial infarction and the influence of direct renin inhibition with aliskiren,” European Journal of Heart Failure, vol. 14, no. 2, pp. 185–192, 2012. View at Publisher · View at Google Scholar · View at Scopus
  5. N. Frey and E. N. Olson, “Cardiac hypertrophy: the good, the bad, and the ugly,” Annual Review of Physiology, vol. 65, pp. 45–79, 2003. View at Publisher · View at Google Scholar · View at Scopus
  6. J. D. Molkentin and G. W. Dorn II, “Cytoplasmic signaling pathways that regulate cardiac hypertrophy,” Annual Review of Physiology, vol. 63, no. 1, pp. 391–426, 2001. View at Publisher · View at Google Scholar · View at Scopus
  7. N. G. Frangogiannis, “Matricellular proteins in cardiac adaptation and disease,” Physiological Reviews, vol. 92, no. 2, pp. 635–688, 2012. View at Publisher · View at Google Scholar · View at Scopus
  8. R. E. Gilbert, “Endothelial loss and repair in the vascular complications of diabetes—mechanisms and therapeutic implications,” Circulation Journal, vol. 77, no. 4, pp. 849–856, 2013. View at Publisher · View at Google Scholar · View at Scopus
  9. B. M. Everett, M. M. Brooks, H. E. A. Vlachos, B. R. Chaitman, R. L. Frye, and D. L. Bhatt, “Troponin and cardiac events in stable ischemic heart disease and diabetes,” The New England Journal of Medicine, vol. 373, no. 7, pp. 610–620, 2015. View at Publisher · View at Google Scholar · View at Scopus
  10. C. Emanueli, A. Caporali, N. Krankel, B. Cristofaro, S. Van Linthout, and P. Madeddu, “Type-2 diabetic Lepr(db/db) mice show a defective microvascular phenotype under basal conditions and an impaired response to angiogenesis gene therapy in the setting of limb ischemia,” Frontiers in Bioscience, vol. 12, pp. 2003–2012, 2007. View at Publisher · View at Google Scholar · View at Scopus
  11. M. A. Pfeffer, B. Claggett, R. Diaz et al., “Lixisenatide in patients with type 2 diabetes and acute coronary syndrome,” The New England Journal of Medicine, vol. 373, no. 23, pp. 2247–2257, 2015. View at Publisher · View at Google Scholar · View at Scopus
  12. H. Suzuki, Y. Kayama, M. Sakamoto et al., “Arachidonate 12/15-lipoxygenase-induced inflammation and oxidative stress are involved in the development of diabetic cardiomyopathy,” Diabetes, vol. 64, no. 2, pp. 618–630, 2015. View at Publisher · View at Google Scholar · View at Scopus
  13. K. A. Connelly, D. J. Kelly, Y. Zhang et al., “Functional, structural and molecular aspects of diastolic heart failure in the diabetic (mRen-2)27 rat,” Cardiovascular Research, vol. 76, no. 2, pp. 280–291, 2007. View at Publisher · View at Google Scholar · View at Scopus
  14. M. Rajesh, P. Mukhopadhyay, S. Btkai et al., “Cannabidiol attenuates cardiac dysfunction, oxidative stress, fibrosis, and inflammatory and cell death signaling pathways in diabetic cardiomyopathy,” Journal of the American College of Cardiology, vol. 56, no. 25, pp. 2115–2125, 2010. View at Publisher · View at Google Scholar · View at Scopus
  15. E. J. Anderson, A. P. Kypson, E. Rodriguez, C. A. Anderson, E. J. Lehr, and P. D. Neufer, “substrate-specific derangements in mitochondrial metabolism and redox balance in the atrium of the type 2 diabetic human heart,” Journal of the American College of Cardiology, vol. 54, no. 20, pp. 1891–1898, 2009. View at Publisher · View at Google Scholar · View at Scopus
  16. E. Braunwald, “Biomarkers in heart failure,” The New England Journal of Medicine, vol. 358, no. 20, pp. 2148–2159, 2008. View at Publisher · View at Google Scholar
  17. V. Parra, H. E. Verdejo, M. Iglewski et al., “Insulin stimulates mitochondrial fusion and function in cardiomyocytes via the Akt-mTOR-NFκB-Opa-1 signaling pathway,” Diabetes, vol. 63, no. 1, pp. 75–88, 2014. View at Publisher · View at Google Scholar · View at Scopus
  18. Y. Matsui, H. Takagi, X. Qu et al., “Distinct roles of autophagy in the heart during ischemia and reperfusion: roles of AMP-activated protein kinase and beclin 1 in mediating autophagy,” Circulation Research, vol. 100, no. 6, pp. 914–922, 2007. View at Publisher · View at Google Scholar · View at Scopus
  19. Q. M. Nguyen, S. R. Sinivasan, J.-H. Xu, W. Chen, and G. S. Berenson, “Changes in risk variables of metabolic syndrome since childhood in pre-diabetic and type 2 diabetic subjects. The Bogalusa Heart Study,” Diabetes Care, vol. 31, no. 10, pp. 2044–2049, 2008. View at Publisher · View at Google Scholar · View at Scopus
  20. T. Miki, T. Itoh, D. Sunaga, and T. Miura, “Effects of diabetes on myocardial infarct size and cardioprotection by preconditioning and postconditioning,” Cardiovascular Diabetology, vol. 11, article 67, 2012. View at Publisher · View at Google Scholar · View at Scopus
  21. B. Drenger, I. A. Ostrovsky, M. Barak, Y. Nechemia-Arbely, E. Ziv, and J. H. Axelrod, “Diabetes blockade of sevoflurane postconditioning is not restored by insulin in the rat heart: phosphorylated signal transducer and activator of transcription 3- and phosphatidylinositol 3-kinase-mediated inhibition,” Anesthesiology—The Journal of the American Society of Anesthesiologists, vol. 114, no. 6, pp. 1364–1372, 2011. View at Publisher · View at Google Scholar · View at Scopus
  22. P. Ferdinandy, D. J. Hausenloy, G. Heusch, G. F. Baxter, and R. Schulz, “Interaction of risk factors, comorbidities, and comedications with ischemia/reperfusion injury and cardioprotection by preconditioning, postconditioning, and remote conditioning,” Pharmacological reviews, vol. 66, no. 4, pp. 1142–1174, 2014. View at Publisher · View at Google Scholar · View at Scopus
  23. D. J. Hausenloy, S. Lecour, and D. M. Yellon, “Reperfusion injury salvage kinase and survivor activating factor enhancement prosurvival signaling pathways in ischemic postconditioning: two sides of the same coin,” Antioxidants & Redox Signaling, vol. 14, no. 5, pp. 893–907, 2011. View at Publisher · View at Google Scholar · View at Scopus
  24. N. Ghaboura, S. Tamareille, P.-H. Ducluzeau et al., “Diabetes mellitus abrogates erythropoietin-induced cardioprotection against ischemic-reperfusion injury by alteration of the RISK/GSK-3β signaling,” Basic Research in Cardiology, vol. 106, no. 1, pp. 147–162, 2011. View at Publisher · View at Google Scholar · View at Scopus
  25. S. Lecour, “Activation of the protective Survivor Activating Factor Enhancement (SAFE) pathway against reperfusion injury: does it go beyond the RISK pathway?” Journal of Molecular and Cellular Cardiology, vol. 47, no. 1, pp. 32–40, 2009. View at Publisher · View at Google Scholar · View at Scopus
  26. C. Zhuo, Y. Wang, X. Wang, Y. Wang, and Y. Chen, “Cardioprotection by ischemic postconditioning is abolished in depressed rats: role of Akt and signal transducer and activator of transcription-3,” Molecular and Cellular Biochemistry, vol. 346, no. 1-2, pp. 39–47, 2011. View at Publisher · View at Google Scholar · View at Scopus
  27. W. Yi, Y. Sun, E. Gao et al., “Reduced cardioprotective action of adiponectin in high-fat diet–induced type II diabetic mice and its underlying mechanisms,” Antioxidants & Redox Signaling, vol. 15, no. 7, pp. 1779–1788, 2011. View at Publisher · View at Google Scholar · View at Scopus
  28. Y. Wang, E. Gao, L. Tao et al., “AMP-activated protein kinase deficiency enhances myocardial ischemia/reperfusion injury but has minimal effect on the antioxidant/antinitrative protection of adiponectin,” Circulation, vol. 119, no. 6, pp. 835–844, 2009. View at Publisher · View at Google Scholar · View at Scopus
  29. D. L. Eizirik, A. K. Cardozo, and M. Cnop, “The role for endoplasmic reticulum stress in diabetes mellitus,” Endocrine Reviews, vol. 29, no. 1, pp. 42–61, 2008. View at Publisher · View at Google Scholar · View at Scopus
  30. L. Yang, D. Zhao, J. Ren, and J. Yang, “Endoplasmic reticulum stress and protein quality control in diabetic cardiomyopathy,” Biochimica et Biophysica Acta—Molecular Basis of Disease, vol. 1852, no. 2, pp. 209–218, 2015. View at Publisher · View at Google Scholar · View at Scopus
  31. T. Miki, T. Miura, H. Hotta et al., “Endoplasmic reticulum stress in diabetic hearts abolishes erythropoietin-induced myocardial protection by impairment of phospho–glycogen synthase kinase-3β–mediated suppression of mitochondrial permeability transition,” Diabetes, vol. 58, no. 12, pp. 2863–2872, 2009. View at Publisher · View at Google Scholar · View at Scopus
  32. L. A. Barr, Y. Shimizu, J. P. Lambert, C. K. Nicholson, and J. W. Calvert, “Hydrogen sulfide attenuates high fat diet-induced cardiac dysfunction via the suppression of endoplasmic reticulum stress,” Nitric Oxide, vol. 46, pp. 145–156, 2015. View at Publisher · View at Google Scholar · View at Scopus
  33. S. Bai, L. Cheng, Y. Yang et al., “C1q/TNF-related protein 9 protects diabetic rat heart against ischemia reperfusion injury: role of endoplasmic reticulum stress,” Oxidative Medicine and Cellular Longevity, vol. 2016, Article ID 1902025, 14 pages, 2016. View at Publisher · View at Google Scholar
  34. M. Aragno, R. Mastrocola, G. Alloatti et al., “Oxidative stress triggers cardiac fibrosis in the heart of diabetic rats,” Endocrinology, vol. 149, no. 1, pp. 380–388, 2008. View at Publisher · View at Google Scholar · View at Scopus
  35. H. Su, L. Ji, W. Xing et al., “Acute hyperglycaemia enhances oxidative stress and aggravates myocardial ischaemia/reperfusion injury: role of thioredoxin-interacting protein,” Journal of Cellular and Molecular Medicine, vol. 17, no. 1, pp. 181–191, 2013. View at Publisher · View at Google Scholar · View at Scopus
  36. M. H. Ghattas and D. M. Abo-Elmatty, “Association of polymorphic markers of the catalase and superoxide dismutase genes with type 2 diabetes mellitus,” DNA and Cell Biology, vol. 31, no. 11, pp. 1598–1603, 2012. View at Publisher · View at Google Scholar · View at Scopus
  37. P. Lewis, N. Stefanovic, J. Pete et al., “Lack of the antioxidant enzyme glutathione peroxidase-1 accelerates atherosclerosis in diabetic apolipoprotein E-deficient mice,” Circulation, vol. 115, no. 16, pp. 2178–2187, 2007. View at Publisher · View at Google Scholar · View at Scopus
  38. R. Luan, S. Liu, T. Yin et al., “High glucose sensitizes adult cardiomyocytes to ischaemia/reperfusion injury through nitrative thioredoxin inactivation,” Cardiovascular Research, vol. 83, no. 2, pp. 294–302, 2009. View at Publisher · View at Google Scholar · View at Scopus
  39. V. Kain, S. Kumar, and S. L. Sitasawad, “Azelnidipine prevents cardiac dysfunction in streptozotocin-diabetic rats by reducing intracellular calcium accumulation, oxidative stress and apoptosis,” Cardiovascular Diabetology, vol. 10, article no. 97, 2011. View at Publisher · View at Google Scholar · View at Scopus
  40. C. Huang, A. M. Andres, E. P. Ratliff, G. Hernandez, P. Lee, and R. A. Gottlieb, “Preconditioning involves selective mitophagy mediated by parkin and p62/SQSTM1,” PLoS ONE, vol. 6, no. 6, Article ID e20975, 2011. View at Publisher · View at Google Scholar · View at Scopus
  41. A. M. Andres, G. Hernandez, P. Lee et al., “Mitophagy is required for acute cardioprotection by simvastatin,” Antioxidants & Redox Signaling, vol. 21, no. 14, pp. 1960–1973, 2014. View at Publisher · View at Google Scholar · View at Scopus
  42. S. Kobayashi, X. Xu, K. Chen, and Q. Liang, “Suppression of autophagy is protective in high glucose-induced cardiomyocyte injury,” Autophagy, vol. 8, no. 4, pp. 577–592, 2012. View at Publisher · View at Google Scholar · View at Scopus
  43. J. Li, S. Rohailla, N. Gelber et al., “MicroRNA-144 is a circulating effector of remote ischemic preconditioning,” Basic Research in Cardiology, vol. 109, no. 5, Article ID 423, 2014. View at Publisher · View at Google Scholar · View at Scopus
  44. T. Baranyai, C. T. Nagy, G. Koncsos et al., “Acute hyperglycemia abolishes cardioprotection by remote ischemic perconditioning,” Cardiovascular Diabetology, vol. 14, no. 1, article 151, 2015. View at Publisher · View at Google Scholar · View at Scopus
  45. K. Raedschelders, D. M. Ansley, and D. D. Y. Chen, “The cellular and molecular origin of reactive oxygen species generation during myocardial ischemia and reperfusion,” Pharmacology and Therapeutics, vol. 133, no. 2, pp. 230–255, 2012. View at Publisher · View at Google Scholar · View at Scopus
  46. J. L. Carson, P. M. Scholz, A. Y. Chen, E. D. Peterson, J. Gold, and S. H. Schneider, “Diabetes mellitus increases short-term mortality and morbidity in patients undergoing coronary artery bypass graft surgery,” Journal of the American College of Cardiology, vol. 40, no. 3, pp. 418–423, 2002. View at Publisher · View at Google Scholar · View at Scopus
  47. X. Du, D. Edelstein, S. Obici, N. Higham, M.-H. Zou, and M. Brownlee, “Insulin resistance reduces arterial prostacyclin synthase and eNOS activities by increasing endothelial fatty acid oxidation,” The Journal of Clinical Investigation, vol. 116, no. 4, pp. 1071–1080, 2006. View at Publisher · View at Google Scholar · View at Scopus
  48. G. Orasanu and J. Plutzky, “The pathologic continuum of diabetic vascular disease,” Journal of the American College of Cardiology, vol. 53, no. 5, pp. S35–S42, 2009. View at Publisher · View at Google Scholar · View at Scopus
  49. T. Yokota, S. Kinugawa, K. Hirabayashi et al., “Oxidative stress in skeletal muscle impairs mitochondrial respiration and limits exercise capacity in type 2 diabetic mice,” American Journal of Physiology—Heart and Circulatory Physiology, vol. 297, no. 3, pp. H1069–H1077, 2009. View at Publisher · View at Google Scholar · View at Scopus
  50. S. Tanguy, J. De Leiris, S. Besse, and F. Boucher, “Ageing exacerbates the cardiotoxicity of hydrogen peroxide through the Fenton reaction in rats,” Mechanisms of Ageing and Development, vol. 124, no. 2, pp. 229–235, 2003. View at Publisher · View at Google Scholar · View at Scopus
  51. S.-I. Yamagishi, D. Edelstein, X.-L. Du, Y. Kaneda, M. Guzmán, and M. Brownlee, “Leptin induces mitochondrial superoxide production and monocyte chemoattractant protein-1 expression in aortic endothelial cells by increasing fatty acid oxidation via protein kinase A,” The Journal of Biological Chemistry, vol. 276, no. 27, pp. 25096–25100, 2001. View at Publisher · View at Google Scholar · View at Scopus
  52. J. Y. Lee, K. H. Sohn, S. H. Rhee, and D. Hwang, “Saturated fatty acids, but not unsaturated fatty acids, induce the expression of cyclooxygenase-2 mediated through toll-like receptor 4,” Journal of Biological Chemistry, vol. 276, no. 20, pp. 16683–16689, 2001. View at Publisher · View at Google Scholar · View at Scopus
  53. N. Coudronniere, M. Villalba, N. Englund, and A. Altman, “NF-kappa B activation induced by T cell receptor/CD28 costimulation is mediated by protein kinase C-theta,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 7, pp. 3394–3399, 2000. View at Google Scholar · View at Scopus
  54. R. Ananthakrishnan, M. Kaneko, Y. C. Hwang et al., “Aldose reductase mediates myocardial ischemia-reperfusion injury in part by opening mitochondrial permeability transition pore,” American Journal of Physiology—Heart and Circulatory Physiology, vol. 296, no. 2, pp. H333–H341, 2009. View at Publisher · View at Google Scholar · View at Scopus
  55. W. H. Tang, G. M. Kravtsov, M. Sauert et al., “Polyol pathway impairs the function of SERCA and RyR in ischemic-reperfused rat hearts by increasing oxidative modifications of these proteins,” Journal of Molecular and Cellular Cardiology, vol. 49, no. 1, pp. 58–69, 2010. View at Publisher · View at Google Scholar · View at Scopus
  56. C.-A. Chen, T.-Y. Wang, S. Varadharaj et al., “S-glutathionylation uncouples eNOS and regulates its cellular and vascular function,” Nature, vol. 468, no. 7327, pp. 1115–1118, 2010. View at Publisher · View at Google Scholar · View at Scopus
  57. R. M. Maalouf, A. A. Eid, Y. C. Gorin et al., “Nox4-derived reactive oxygen species mediate cardiomyocyte injury in early type 1 diabetes,” American Journal of Physiology—Cell Physiology, vol. 302, no. 3, pp. C597–C604, 2012. View at Publisher · View at Google Scholar · View at Scopus
  58. T. Okazaki, H. Otani, T. Shimazu et al., “Reversal of inducible nitric oxide synthase uncoupling unmasks tolerance to ischemia/reperfusion injury in the diabetic rat heart,” Journal of Molecular and Cellular Cardiology, vol. 50, no. 3, pp. 534–544, 2011. View at Publisher · View at Google Scholar · View at Scopus
  59. G. Ashrafi and T. L. Schwarz, “The pathways of mitophagy for quality control and clearance of mitochondria,” Cell Death & Differentiation, vol. 20, no. 1, pp. 31–42, 2013. View at Publisher · View at Google Scholar · View at Scopus
  60. M. P. Murphy, “Induction of mitochondrial ROS production by electrophilic lipids: a new pathway of redox signaling?” American Journal of Physiology—Heart and Circulatory Physiology, vol. 290, no. 5, pp. H1754–H1755, 2006. View at Publisher · View at Google Scholar · View at Scopus
  61. S. Wullschleger, R. Loewith, and M. N. Hall, “TOR signaling in growth and metabolism,” Cell, vol. 124, no. 3, pp. 471–484, 2006. View at Publisher · View at Google Scholar · View at Scopus
  62. S. C. Johnson, P. S. Rabinovitch, and M. Kaeberlein, “MTOR is a key modulator of ageing and age-related disease,” Nature, vol. 493, no. 7432, pp. 338–345, 2013. View at Publisher · View at Google Scholar · View at Scopus
  63. M. Laplante and D. M. Sabatini, “Regulation of mTORC1 and its impact on gene expression at a glance,” Journal of Cell Science, vol. 126, no. 8, pp. 1713–1719, 2013. View at Publisher · View at Google Scholar · View at Scopus
  64. D. Zhang, R. Contu, M. V. G. Latronico et al., “MTORC1 regulates cardiac function and myocyte survival through 4E-BP1 inhibition in mice,” Journal of Clinical Investigation, vol. 120, no. 10, p. 3735, 2010. View at Publisher · View at Google Scholar · View at Scopus
  65. M. Laplante and D. M. Sabatini, “MTOR signaling in growth control and disease,” Cell, vol. 149, no. 2, pp. 274–293, 2012. View at Publisher · View at Google Scholar · View at Scopus
  66. T. Aoyagi, Y. Kusakari, C.-Y. Xiao et al., “Cardiac mTOR protects the heart against ischemia-reperfusion injury,” American Journal of Physiology—Heart and Circulatory Physiology, vol. 303, no. 1, pp. H75–H85, 2012. View at Publisher · View at Google Scholar · View at Scopus
  67. H. P. Glazer, R. M. Osipov, R. T. Clements, F. W. Sellke, and C. Bianchi, “Hypercholesterolemia is associated with hyperactive cardiac mTORC1 and mTORC2 signaling,” Cell Cycle, vol. 8, no. 11, pp. 1738–1746, 2009. View at Publisher · View at Google Scholar · View at Scopus
  68. S. C. Land and A. R. Tee, “Hypoxia-inducible factor 1α is regulated by the mammalian target of rapamycin (mTOR) via an mTOR signaling motif,” Journal of Biological Chemistry, vol. 282, no. 28, pp. 20534–20543, 2007. View at Publisher · View at Google Scholar · View at Scopus
  69. J.-W. Park, W.-H. Kim, S.-H. Shin et al., “Visfatin exerts angiogenic effects on human umbilical vein endothelial cells through the mTOR signaling pathway,” Biochimica et Biophysica Acta—Molecular Cell Research, vol. 1813, no. 5, pp. 763–771, 2011. View at Publisher · View at Google Scholar · View at Scopus
  70. P. C. Schenkel, A. M. V. Tavares, R. O. Fernandes et al., “Time course of hydrogen peroxide-thioredoxin balance and its influence on the intracellular signalling in myocardial infarction,” Experimental Physiology, vol. 97, no. 6, pp. 741–749, 2012. View at Publisher · View at Google Scholar · View at Scopus
  71. A. G. Rajapakse, G. Yepuri, J. M. Carvas et al., “Hyperactive S6K1 mediates oxidative stress and endothelial dysfunction in aging: inhibition by resveratrol,” PLoS ONE, vol. 6, no. 4, Article ID e19237, 2011. View at Publisher · View at Google Scholar · View at Scopus
  72. Z. Z. Chong, Y. C. Shang, and K. Maiese, “Cardiovascular disease and mTOR signaling,” Trends in Cardiovascular Medicine, vol. 21, no. 5, pp. 151–155, 2011. View at Publisher · View at Google Scholar · View at Scopus
  73. H. Yao, X. Han, and X. Han, “The cardioprotection of the insulin-mediated PI3K/Akt/mTOR signaling pathway,” American Journal of Cardiovascular Drugs, vol. 14, no. 6, pp. 433–442, 2014. View at Publisher · View at Google Scholar · View at Scopus
  74. R. Si, L. Tao, H. F. Zhang et al., “Survivin: a novel player in insulin cardioprotection against myocardial ischemia/reperfusion injury,” Journal of Molecular and Cellular Cardiology, vol. 50, no. 1, pp. 16–24, 2011. View at Publisher · View at Google Scholar · View at Scopus
  75. V. Lemaître, A. J. Dabo, and J. D'Armiento, “Cigarette smoke components induce matrix metalloproteinase-1 in aortic endothelial cells through inhibition of mTOR signaling,” Toxicological Sciences, vol. 123, no. 2, pp. 542–549, 2011. View at Publisher · View at Google Scholar · View at Scopus
  76. S. Fourcade, I. Ferrer, and A. Pujol, “Oxidative stress, mitochondrial and proteostasis malfunction in adrenoleukodystrophy: a paradigm for axonal degeneration,” Free Radical Biology and Medicine, vol. 88, pp. 18–29, 2015. View at Publisher · View at Google Scholar · View at Scopus
  77. K. Maiese, Z. Z. Chong, Y. C. Shang, and S. Wang, “Translating cell survival and cell longevity into treatment strategies with SIRT1,” Romanian Journal of Morphology and Embryology, vol. 52, no. 4, pp. 1173–1185, 2011. View at Google Scholar · View at Scopus
  78. R.-H. Wang, H.-S. Kim, C. Xiao, X. Xu, O. Gavrilova, and C.-X. Deng, “Hepatic Sirt1 deficiency in mice impairs mTorc2/Akt signaling and results in hyperglycemia, oxidative damage, and insulin resistance,” The Journal of Clinical Investigation, vol. 121, no. 11, pp. 4477–4490, 2011. View at Publisher · View at Google Scholar · View at Scopus
  79. S. C. Ranieri, S. Fusco, E. Panieri et al., “Mammalian life-span determinant p66shcA mediates obesity-induced insulin resistance,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 30, pp. 13420–13425, 2010. View at Publisher · View at Google Scholar · View at Scopus
  80. J. C. Drake, S. E. Alway, J. M. Hollander, and D. L. Williamson, “AICAR treatment for 14 days normalizes obesity-induced dysregulation of TORC1 signaling and translational capacity in fasted skeletal muscle,” American Journal of Physiology—Regulatory Integrative and Comparative Physiology, vol. 299, no. 6, pp. R1546–R1554, 2010. View at Publisher · View at Google Scholar · View at Scopus
  81. S. Turdi, M. R. Kandadi, J. Zhao, A. F. Huff, M. Du, and J. Ren, “Deficiency in AMP-activated protein kinase exaggerates high fat diet-induced cardiac hypertrophy and contractile dysfunction,” Journal of Molecular and Cellular Cardiology, vol. 50, no. 4, pp. 712–722, 2011. View at Publisher · View at Google Scholar · View at Scopus
  82. R. Guo, Y. Zhang, S. Turdi, and J. Ren, “Adiponectin knockout accentuates high fat diet-induced obesity and cardiac dysfunction: role of autophagy,” Biochimica et Biophysica Acta - Molecular Basis of Disease, vol. 1832, no. 8, pp. 1136–1148, 2013. View at Publisher · View at Google Scholar · View at Scopus
  83. S. Sciarretta, P. Zhai, D. Shao et al., “Rheb is a critical regulator of autophagy during myocardial ischemia: pathophysiological implications in obesity and metabolic syndrome,” Circulation, vol. 125, no. 9, pp. 1134–1146, 2012. View at Publisher · View at Google Scholar · View at Scopus
  84. L. Yang, J.-Y. Gao, J. Ma et al., “Cardiac-specific overexpression of metallothionein attenuates myocardial remodeling and contractile dysfunction in l-NAME-induced experimental hypertension: role of autophagy regulation,” Toxicology Letters, vol. 237, no. 2, pp. 121–132, 2015. View at Publisher · View at Google Scholar · View at Scopus
  85. C. H. Jung, C. B. Jun, S.-H. Ro et al., “ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery,” Molecular Biology of the Cell, vol. 20, no. 7, pp. 1992–2003, 2009. View at Publisher · View at Google Scholar · View at Scopus
  86. A. De Waha, A. Dibra, S. Kufner et al., “Long-term outcome after sirolimus-eluting stents versus bare metal stents in patients with Diabetes mellitus: a patient-level meta-analysis of randomized trials,” Clinical Research in Cardiology, vol. 100, no. 7, pp. 561–570, 2011. View at Publisher · View at Google Scholar · View at Scopus
  87. A. Das, F. N. Salloum, D. Durrant, R. Ockaili, and R. C. Kukreja, “Rapamycin protects against myocardial ischemia–reperfusion injury through JAK2–STAT3 signaling pathway,” Journal of Molecular and Cellular Cardiology, vol. 53, no. 6, pp. 858–869, 2012. View at Publisher · View at Google Scholar · View at Scopus
  88. A. Das, F. N. Salloum, S. M. Filippone et al., “Inhibition of mammalian target of rapamycin protects against reperfusion injury in diabetic heart through STAT3 signaling,” Basic Research in Cardiology, vol. 110, no. 3, 2015. View at Publisher · View at Google Scholar · View at Scopus
  89. T. Aoyagi, J. K. Higa, H. Aoyagi, N. Yorichika, B. K. Shimada, and T. Matsui, “Cardiac mTOR rescues the detrimental effects of diet-induced obesity in the heart after ischemia-reperfusion,” American Journal of Physiology—Heart and Circulatory Physiology, vol. 308, no. 12, pp. H1530–H1539, 2015. View at Publisher · View at Google Scholar · View at Scopus
  90. M. Zhang, D. Sun, S. Li et al., “Lin28a protects against cardiac ischaemia/reperfusion injury in diabetic mice through the insulin-PI3K-mTOR pathway,” Journal of Cellular and Molecular Medicine, vol. 19, no. 6, pp. 1174–1182, 2015. View at Publisher · View at Google Scholar · View at Scopus
  91. Z. Lu, X. Xu, X. Hu et al., “PGC-1α regulates expression of myocardial mitochondrial antioxidants and myocardial oxidative stress after chronic systolic overload,” Antioxidants & Redox Signaling, vol. 13, no. 7, pp. 1011–1022, 2010. View at Publisher · View at Google Scholar · View at Scopus
  92. J. T. Cunningham, J. T. Rodgers, D. H. Arlow, F. Vazquez, V. K. Mootha, and P. Puigserver, “mTOR controls mitochondrial oxidative function through a YY1-PGC-1α transcriptional complex,” Nature, vol. 450, no. 7170, pp. 736–740, 2007. View at Publisher · View at Google Scholar · View at Scopus
  93. R. Humar, F. N. Kiefer, H. Berns, T. J. Resink, and E. J. Battegay, “Hypoxia enhances vascular cell proliferation and angiogenesis in vitro via rapamycin (mTOR)-dependent signaling,” FASEB Journal, vol. 16, no. 8, pp. 771–780, 2002. View at Publisher · View at Google Scholar · View at Scopus
  94. S. G. Miriuka, V. Rao, M. Peterson et al., “mTOR inhibition induces endothelial progenitor cell death,” American Journal of Transplantation, vol. 6, no. 9, pp. 2069–2079, 2006. View at Publisher · View at Google Scholar · View at Scopus
  95. R. Bernardi, I. Guernah, D. Jin et al., “PML inhibits HIF-1α translation and neoangiogenesis through repression of mTOR,” Nature, vol. 442, no. 7104, pp. 779–785, 2006. View at Publisher · View at Google Scholar · View at Scopus
  96. M. Völkers, M. H. Konstandin, S. Doroudgar et al., “Mechanistic target of rapamycin complex 2 protects the heart from ischemic damage,” Circulation, vol. 128, no. 19, pp. 2132–2144, 2013. View at Publisher · View at Google Scholar · View at Scopus
  97. C. C. Thoreen and D. M. Sabatini, “Rapamycin inhibits mTORC1, but not completely,” Autophagy, vol. 5, no. 5, pp. 725–726, 2009. View at Publisher · View at Google Scholar · View at Scopus
  98. C. Wagner, D. Tillack, G. Simonis, R. H. Strasser, and C. Weinbrenner, “Ischemic post-conditioning reduces infarct size of the in vivo rat heart: role of PI3-K, mTOR, GSK-3β, and apoptosis,” Molecular and Cellular Biochemistry, vol. 339, no. 1-2, pp. 135–147, 2010. View at Publisher · View at Google Scholar · View at Scopus
  99. R. Pal, M. Palmieri, J. A. Loehr et al., “Src-dependent impairment of autophagy by oxidative stress in a mouse model of Duchenne muscular dystrophy,” Nature Communications, vol. 5, article 4425, 2014. View at Publisher · View at Google Scholar · View at Scopus
  100. P. Shende, I. Plaisance, C. Morandi et al., “Cardiac raptor ablation impairs adaptive hypertrophy, alters metabolic gene expression, and causes heart failure in mice,” Circulation, vol. 123, no. 10, pp. 1073–1082, 2011. View at Publisher · View at Google Scholar · View at Scopus
  101. P. C. Schenkel, A. M. V. Tavares, R. O. Fernandes et al., “Redox-sensitive prosurvival and proapoptotic protein expression in the myocardial remodeling post-infarction in rats,” Molecular and Cellular Biochemistry, vol. 341, no. 1-2, pp. 1–8, 2010. View at Publisher · View at Google Scholar · View at Scopus
  102. E. Martínez-Martínez, R. Jurado-López, M. Valero-Muñoz et al., “Leptin induces cardiac fibrosis through galectin-3, mTOR and oxidative stress: potential role in obesity,” Journal of Hypertension, vol. 32, no. 5, pp. 1104–1114, 2014. View at Publisher · View at Google Scholar · View at Scopus
  103. J. Zhang, J. Kim, A. Alexander et al., “A tuberous sclerosis complex signalling node at the peroxisome regulates mTORC1 and autophagy in response to ROS,” Nature Cell Biology, vol. 15, no. 10, pp. 1186–1196, 2013. View at Publisher · View at Google Scholar · View at Scopus
  104. F. Vigneron, P. Dos Santos, S. Lemoine et al., “GSK-3β at the crossroads in the signalling of heart preconditioning: implication of mTOR and Wnt pathways,” Cardiovascular Research, vol. 90, no. 1, pp. 49–56, 2011. View at Publisher · View at Google Scholar · View at Scopus
  105. S. Sen, B. K. Kundu, H. C. Wu et al., “Glucose regulation of load-induced mTOR signaling and ER stress in mammalian heart,” Journal of the American Heart Association, vol. 2, no. 3, Article ID e004796, 2013. View at Publisher · View at Google Scholar
  106. J. W. Calvert, S. Gundewar, S. Jha et al., “Acute metformin therapy confers cardioprotection against myocardial infarction via AMPK-eNOS- mediated signaling,” Diabetes, vol. 57, no. 3, pp. 696–705, 2008. View at Publisher · View at Google Scholar · View at Scopus
  107. X. Xu, Z. Lu, J. Fassett et al., “Metformin protects against systolic overload-induced heart failure independent of AMP-activated protein kinase α2,” Hypertension, vol. 63, no. 4, pp. 723–728, 2014. View at Publisher · View at Google Scholar · View at Scopus
  108. M. Hu, P. Ye, H. Liao, M. Chen, and F. Yang, “Metformin protects H9C2 cardiomyocytes from high-glucose and hypoxia/reoxygenation injury via inhibition of reactive oxygen species generation and inflammatory responses: role of AMPK and JNK,” Journal of Diabetes Research, vol. 2016, Article ID 2961954, 9 pages, 2016. View at Publisher · View at Google Scholar · View at Scopus
  109. D. Kukidome, T. Nishikawa, K. Sonoda et al., “Activation of AMP-activated protein kinase reduces hyperglycemia-induced mitochondrial reactive oxygen species production and promotes mitochondrial biogenesis in human umbilical vein endothelial cells,” Diabetes, vol. 55, no. 1, pp. 120–127, 2006. View at Publisher · View at Google Scholar · View at Scopus
  110. X.-F. Wang, J.-Y. Zhang, L. Li, X.-Y. Zhao, H.-L. Tao, and L. Zhang, “Metformin improves cardiac function in rats via activation of AMP-activated protein kinase,” Clinical and Experimental Pharmacology and Physiology, vol. 38, no. 2, pp. 94–101, 2011. View at Publisher · View at Google Scholar · View at Scopus
  111. E. P. Daskalopoulos, C. Dufeys, L. Bertrand, C. Beauloye, and S. Horman, “AMPK in cardiac fibrosis and repair: actions beyond metabolic regulation,” Journal of Molecular and Cellular Cardiology, vol. 91, pp. 188–200, 2016. View at Publisher · View at Google Scholar · View at Scopus
  112. S.-I. Imai and L. Guarente, “NAD+ and sirtuins in aging and disease,” Trends in Cell Biology, vol. 24, no. 8, pp. 464–471, 2014. View at Publisher · View at Google Scholar · View at Scopus
  113. G. Donmez and L. Guarente, “Aging and disease: connections to sirtuins,” Aging Cell, vol. 9, no. 2, pp. 285–290, 2010. View at Publisher · View at Google Scholar · View at Scopus
  114. L. Zhong and R. Mostoslavsky, “Fine tuning our cellular factories: sirtuins in mitochondrial biology,” Cell Metabolism, vol. 13, no. 6, pp. 621–626, 2011. View at Publisher · View at Google Scholar · View at Scopus
  115. S.-B. Wu, Y.-T. Wu, T.-P. Wu, and Y.-H. Wei, “Role of AMPK-mediated adaptive responses in human cells with mitochondrial dysfunction to oxidative stress,” Biochimica et Biophysica Acta—General Subjects, vol. 1840, no. 4, pp. 1331–1344, 2014. View at Publisher · View at Google Scholar · View at Scopus
  116. F. Hong, M. D. Larrea, C. Doughty, D. J. Kwiatkowski, R. Squillace, and J. M. Slingerland, “mTOR-raptor binds and activates SGK1 to regulate p27 phosphorylation,” Molecular Cell, vol. 30, no. 6, pp. 701–711, 2008. View at Publisher · View at Google Scholar · View at Scopus
  117. K. Maiese, “Targeting molecules to medicine with mTOR, autophagy and neurodegenerative disorders,” British Journal of Clinical Pharmacology, vol. 82, no. 5, pp. 1245–1266, 2016. View at Publisher · View at Google Scholar · View at Scopus
  118. J. M. Peterson, Z. Wei, M. M. Seldin, M. S. Byerly, S. Aja, and G. W. Wong, “CTRP9 transgenic mice are protected from diet-induced obesity and metabolic dysfunction,” American Journal of Physiology—Regulatory Integrative and Comparative Physiology, vol. 305, no. 5, pp. R522–R533, 2013. View at Publisher · View at Google Scholar · View at Scopus
  119. Z. Wei, X. Lei, P. S. Petersen, S. Aja, and G. W. Wong, “Targeted deletion of C1q/TNF-related protein 9 increases food intake, decreases insulin sensitivity, and promotes hepatic steatosis in mice,” American Journal of Physiology—Endocrinology and Metabolism, vol. 306, no. 7, pp. E779–E790, 2014. View at Publisher · View at Google Scholar · View at Scopus
  120. H. Su, Y. Yuan, X.-M. Wang et al., “Inhibition of CTRP9, a novel and cardiac-abundantly expressed cell survival molecule, by TNFα-initiated oxidative signaling contributes to exacerbated cardiac injury in diabetic mice,” Basic Research in Cardiology, vol. 108, no. 1, article no. 315, 2013. View at Publisher · View at Google Scholar · View at Scopus
  121. T. Kambara, R. Shibata, K. Ohashi et al., “C1q/tumor necrosis factor-related protein 9 protects against acute myocardial injury through an adiponectin receptor I-AMPK-dependent mechanism,” Molecular and Cellular Biology, vol. 35, no. 12, pp. 2173–2185, 2015. View at Publisher · View at Google Scholar · View at Scopus
  122. T. Kambara, K. Ohashi, R. Shibata et al., “CTRP9 protein protects against myocardial injury following ischemia-reperfusion through AMP-activated protein kinase (AMPK)-dependent mechanism,” Journal of Biological Chemistry, vol. 287, no. 23, pp. 18965–18973, 2012. View at Publisher · View at Google Scholar · View at Scopus
  123. Y. Fang, R. Westbrook, C. Hill et al., “Duration of rapamycin treatment has differential effects on metabolism in mice,” Cell Metabolism, vol. 17, no. 3, pp. 456–462, 2013. View at Publisher · View at Google Scholar · View at Scopus
  124. V. P. Houde, S. Brûlé, W. T. Festuccia et al., “Chronic rapamycin treatment causes glucose intolerance and hyperlipidemia by upregulating hepatic gluconeogenesis and impairing lipid deposition in adipose tissue,” Diabetes, vol. 59, no. 6, pp. 1338–1348, 2010. View at Publisher · View at Google Scholar · View at Scopus
  125. L. Yu, C. K. McPhee, L. Zheng et al., “Termination of autophagy and reformation of lysosomes regulated by mTOR,” Nature, vol. 465, no. 7300, pp. 942–946, 2010. View at Publisher · View at Google Scholar · View at Scopus
  126. Y.-G. Gangloff, M. Mueller, S. G. Dann et al., “Disruption of the mouse mTOR gene leads to early postimplantation lethality and prohibits embryonic stem cell development,” Molecular and Cellular Biology, vol. 24, no. 21, pp. 9508–9516, 2004. View at Publisher · View at Google Scholar · View at Scopus
  127. M. Murakami, T. Ichisaka, M. Maeda et al., “mTOR is essential for growth and proliferation in early mouse embryos and embryonic stem cells,” Molecular and Cellular Biology, vol. 24, no. 15, pp. 6710–6718, 2004. View at Publisher · View at Google Scholar · View at Scopus
  128. D. A. Guertin, D. M. Stevens, C. C. Thoreen et al., “Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCα, but not S6K1,” Developmental Cell, vol. 11, no. 6, pp. 859–871, 2006. View at Publisher · View at Google Scholar · View at Scopus
  129. Y. Rong, C. K. McPhee, S. Deng et al., “Spinster is required for autophagic lysosome reformation and mTOR reactivation following starvation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 19, pp. 7826–7831, 2011. View at Publisher · View at Google Scholar · View at Scopus