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Experimental Diabetes Research
Volume 2012 (2012), Article ID 654904, 12 pages
http://dx.doi.org/10.1155/2012/654904
Review Article

Cardiac Insulin Resistance and MicroRNA Modulators

1Department of Internal Medicine, School of Medicine, University of Missouri, Columbia, MO 65212, USA
2Department of Nutrition and Exercise Physiology, School of Medicine, University of Missouri, Columbia, MO 65212, USA
3Diabetes and Cardiovascular Laboratory, School of Medicine, University of Missouri, Columbia, MO 65212, USA
4Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201, USA
5Department of Medical Pharmacology and Physiology, School of Medicine, University of Missouri, One Hospital Drive, Columbia, MO 65212, USA

Received 8 July 2011; Accepted 22 July 2011

Academic Editor: Jun Ren

Copyright © 2012 Lakshmi Pulakat 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. J. R. Sowers, A. Whaley-Connell, and M. R. Hayden, “The role of overweight and obesity in the cardiorenal syndrome,” CardioRenal Medicine, vol. 1, pp. 5–12, 2011. View at Google Scholar
  2. L. Pulakat, V. G. DeMarco, A. Whaley-Connell, and J. R. Sowers, “The impact of overnutrition on insulin metabolic signaling in the heart and the kidney,” CardioRenal Medicine, vol. 2, pp. 102–112, 2011. View at Google Scholar
  3. J. R. Sowers, “Hypertension, angiotensin II, and oxidative stress,” The New England Journal of Medicine, vol. 346, no. 25, pp. 1999–2001, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  4. J. R. Sowers, “Metabolic risk factors and renal disease,” Kidney International, vol. 71, no. 8, pp. 719–720, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  5. A. Galassi, K. Reynolds, and J. He, “Metabolic syndrome and risk of cardiovascular disease: a meta-analysis,” American Journal of Medicine, vol. 119, no. 10, pp. 812–819, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  6. T. L. Pettman, J. D. Buckley, A. M. Coates, G. M. H. Misan, J. Petkov, and P. R. C. Howe, “Prevalence and interrelationships between cardio-metabolic risk factors in abdominally obese individuals,” Metabolic Syndrome and Related Disorders, vol. 7, no. 1, pp. 31–36, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  7. G. E. Crichton, J. Bryan, J. Buckley, and K. J. Murphy, “Dairy consumption and metabolic syndrome: a systematic review of findings and methodological issues,” Obesity Reviews, vol. 12, no. 5, pp. e190–e201, 2011. View at Google Scholar
  8. L. de Koning , V. S. Malik, E. B. Rimm, W. C. Willett, and F. B. Hu, “Sugar-sweetened and artificially sweetened beverage consumption and risk of type 2 diabetes in men,” The American Journal of Clinical Nutrition, vol. 93, no. 6, pp. 1321–1327, 2011. View at Google Scholar
  9. L. G. Gillingham, S. Harris-Janz, and P. J. Jones, “Dietary monounsaturated fatty acids are protective against metabolic syndrome and cardiovascular disease risk factors,” Lipids, vol. 46, no. 3, pp. 209–228, 2011. View at Google Scholar
  10. P. W. Siri-Tarino, Q. Sun, F. B. Hu, and R. M. Krauss, “Saturated fat, carbohydrate, and cardiovascular disease,” American Journal of Clinical Nutrition, vol. 91, no. 3, pp. 502–509, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  11. F. B. Hu and W. C. Willett, “Optimal diets for prevention of coronary heart disease,” Journal of the American Medical Association, vol. 288, no. 20, pp. 2569–2578, 2002. View at Publisher · View at Google Scholar · View at Scopus
  12. C. R. Wilson, M. K. Tran, K. L. Salazar, M. E. Young, and H. Taegtmeyer, “Western diet, but not high fat diet, causes derangements of fatty acid metabolism and contractile dysfunction in the heart of Wistar rats,” Biochemical Journal, vol. 406, no. 3, pp. 457–467, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  13. B. P. Sampey, A. M. Vanhoose, H. M. Winfield et al., “Cafeteria diet is a robust model of human metabolic syndrome with liver and adipose inflammation: comparison to high-fat diet,” Obesity, vol. 19, no. 6, pp. 1109–1117, 2011. View at Google Scholar
  14. S. Liu, W. C. Willett, M. J. Stampfer et al., “A prospective study of dietary glycemic load, carbohydrate intake, and risk of coronary heart disease in US women,” American Journal of Clinical Nutrition, vol. 71, no. 6, pp. 1455–1461, 2000. View at Google Scholar · View at Scopus
  15. J. M. Osmond, J. D. Mintz, B. Dalton, and D. W. Stepp, “Obesity increases blood pressure, cerebral vascular remodeling, and severity of stroke in the Zucker rat,” Hypertension, vol. 53, no. 2, pp. 381–386, 2009. View at Publisher · View at Google Scholar · View at PubMed
  16. A. Whaley-Connell and J. R. Sowers, “Hypertension and insulin resistance,” Hypertension, vol. 54, no. 3, pp. 462–464, 2009. View at Google Scholar
  17. F. Tremblay, M. Krebs, L. Dombrowski et al., “Overactivation of S6 kinase 1 as a cause of human insulin resistance during increased amino acid availability,” Diabetes, vol. 54, no. 9, pp. 2674–2684, 2005. View at Publisher · View at Google Scholar
  18. F. Xiao, Z. Huang, H. Li et al., “Leucine deprivation increases hepatic insulin sensitivity via GCN2/mTOR/S6K1 and AMPK pathways,” Diabetes, vol. 60, no. 3, pp. 746–756, 2011. View at Google Scholar
  19. C. Wong and T. H. Marwick, “Obesity cardiomyopathy: pathogenesis and pathophysiology,” Nature Clinical Practice Cardiovascular Medicine, vol. 4, no. 8, pp. 436–443, 2007. View at Publisher · View at Google Scholar · View at PubMed
  20. J. A. Kim, Y. Wei, and J. R. Sowers, “Role of mitochondrial dysfunction in insulin resistance,” Circulation Research, vol. 102, no. 4, pp. 401–414, 2008. View at Publisher · View at Google Scholar · View at PubMed
  21. A. D. de Kloet, E. G. Krause, and S. C. Woods, “The renin angiotensin system and the metabolic syndrome,” Physiology and Behavior, vol. 100, no. 5, pp. 525–534, 2010. View at Publisher · View at Google Scholar · View at PubMed
  22. V. Kotsis, S. Stabouli, S. Papakatsika, Z. Rizos, and G. Parati, “Mechanisms of obesity-induced hypertension,” Hypertension Research, vol. 33, no. 5, pp. 386–393, 2010. View at Publisher · View at Google Scholar · View at PubMed
  23. G. Lastra, J. Habibi, A. T. Whaley-Connell et al., “Direct renin inhibition improves systemic insulin resistance and skeletal muscle glucose transport in a transgenic rodent model of tissue renin overexpression,” Endocrinology, vol. 150, no. 6, pp. 2561–2568, 2009. View at Publisher · View at Google Scholar · View at PubMed
  24. J. Iwanami, M. Mogi, M. Iwai, and M. Horiuchi, “Inhibition of the renin-angiotensin system and target organ protection,” Hypertension Research, vol. 32, no. 4, pp. 229–237, 2009. View at Publisher · View at Google Scholar · View at PubMed
  25. C. M. Werner and M. Böhm, “Review: the therapeutic role of RAS blockade in chronic heart failure,” Therapeutic Advances in Cardiovascular Disease, vol. 2, no. 3, pp. 167–177, 2008. View at Publisher · View at Google Scholar · View at PubMed
  26. T. W. Kurtz, “Beyond the classic angiotensin-receptor-blocker profile,” Nature Clinical Practice Cardiovascular Medicine, vol. 5, supplement 1, pp. S19–S26, 2008. View at Google Scholar
  27. J. L. Grobe, A. P. Mecca, M. Lingis et al., “Prevention of angiotensin II-induced cardiac remodeling by angiotensin-(1-7),” American Journal of Physiology, vol. 292, no. 2, pp. H736–H742, 2007. View at Publisher · View at Google Scholar · View at PubMed
  28. A. Aneja, W. H. W. Tang, S. Bansilal, M. J. Garcia, and M. E. Farkouh, “Diabetic cardiomyopathy: insights into pathogenesis, diagnostic challenges, and therapeutic options,” American Journal of Medicine, vol. 121, no. 9, pp. 748–757, 2008. View at Publisher · View at Google Scholar · View at PubMed
  29. D. M. Allcock and J. R. Sowers, “Best strategies for hypertension management in type 2 diabetes and obesity,” Current Diabetes Reports, vol. 10, no. 2, pp. 139–144, 2010. View at Publisher · View at Google Scholar · View at PubMed
  30. P. Verdecchia, F. Angeli, G. Mazzotta, and G. Reboldi, “Angiotensin converting enzyme inhibitors and angiotensin receptor blockers in the treatment of hypertension: should they be used together?” Current Vascular Pharmacology, vol. 8, no. 6, pp. 742–746, 2010. View at Google Scholar
  31. M. F. B. Braga and L. A. Leiter, “Role of renin-Angiotensin system blockade in patients with diabetes mellitus,” American Journal of Cardiology, vol. 104, no. 6, pp. 835–839, 2009. View at Publisher · View at Google Scholar · View at PubMed
  32. C. Grothusen, D. Divchev, M. Luchtefeld, and B. Schieffer, “Angiotensin II type 1 receptor blockade: high hopes sent back to reality?” Minerva Cardioangiologica, vol. 57, no. 6, pp. 773–785, 2009. View at Google Scholar
  33. J. R. Sowers, L. Raij, I. Jialal et al., “Angiotensin receptor blocker/diuretic combination preserves insulin responses in obese hypertensives,” Journal of Hypertension, vol. 28, no. 8, pp. 1761–1769, 2010. View at Publisher · View at Google Scholar · View at PubMed
  34. W. B. Lau, L. Tao, Y. Wang, R. Li, and X. L. Ma, “Systemic adiponectin malfunction as a risk factor for cardiovascular disease,” Antioxidants & Redox Signaling, vol. 15, no. 7, pp. 1863–1873, 2011. View at Google Scholar
  35. C. Hug and H. F. Lodish, “The role of the adipocyte hormone adiponectin in cardiovascular disease,” Current Opinion in Pharmacology, vol. 5, no. 2, pp. 129–134, 2005. View at Publisher · View at Google Scholar · View at PubMed
  36. M. S. Jamaluddin, S. M. Weakley, Q. Yao, and C. Chen, “Resistin: functional roles and therapeutic considerations for cardiovascular disease,” British Journal of Pharmacology. In press.
  37. L. Pulakat, V. G. Demarco, S. Ardhanari et al., “Adaptive mechanisms to compensate for overnutrition-induced cardiovascular abnormalities,” American Journal of Physiology, Regulatory, Integrative and Comparative Physiology, 2011. In press.
  38. S. Sengupta, T. R. Peterson, and D. M. Sabatini, “Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress,” Molecular Cell, vol. 40, no. 2, pp. 310–322, 2010. View at Publisher · View at Google Scholar · View at PubMed
  39. V. Flati, E. Pasini, G. D'Antona, S. Speca, E. Toniato, and S. Martinotti, “Intracellular mechanisms of metabolism regulation: the role of signaling via the mammalian target of rapamycin pathway and other routes,” American Journal of Cardiology, vol. 101, no. 11, pp. S16–S21, 2008. View at Publisher · View at Google Scholar · View at PubMed
  40. M. Cully and J. Downward, “Translational responses to growth factors and stress,” Biochemical Society Transactions, vol. 37, no. 1, pp. 284–288, 2009. View at Publisher · View at Google Scholar · View at PubMed
  41. C. S. Conn and S. B. Qian, “mTOR signaling in protein homeostasis: less is more?” Cell Cycle, vol. 10, pp. 1940–1947, 2011. View at Google Scholar
  42. P. Kapahi, D. Chen, A. N. Rogers et al., “With TOR, less is more: a key role for the conserved nutrient-sensing TOR pathway in aging,” Cell Metabolism, vol. 11, no. 6, pp. 453–465, 2010. View at Publisher · View at Google Scholar · View at PubMed
  43. K. E. Wellen and C. B. Thompson, “Cellular metabolic stress: considering how cells respond to nutrient excess,” Molecular Cell, vol. 40, no. 2, pp. 323–332, 2010. View at Publisher · View at Google Scholar · View at PubMed
  44. H. Zhou and S. Huang, “The complexes of mammalian target of rapamycin,” Current Protein & Peptide Science, vol. 11, pp. 409–424, 2010. View at Google Scholar
  45. G. P. Diniz, M. L. M. Barreto-Chaves, and M. S. Carneiro-Ramos, “Angiotensin type 1 receptor mediates thyroid hormone-induced cardiomyocyte hypertrophy through the Akt/GSK-3β/mTOR signaling pathway,” Basic Research in Cardiology, vol. 104, no. 6, pp. 653–667, 2009. View at Publisher · View at Google Scholar · View at PubMed
  46. T. M. Marin, K. Keith, B. Davies et al., “Rapamycin reverses hypertrophic cardiomyopathy in a mouse model of LEOPARD syndrome-associated PTPN11 mutation,” Journal of Clinical Investigation, vol. 121, pp. 1026–1043, 2011. View at Google Scholar
  47. M. A. Mueller, F. Beutner, D. Teupser, U. Ceglarek, and J. Thiery, “Prevention of atherosclerosis by the mTOR inhibitor everolimus in LDLR-/- mice despite severe hypercholesterolemia,” Atherosclerosis, vol. 198, no. 1, pp. 39–48, 2008. View at Publisher · View at Google Scholar · View at PubMed
  48. J. R. Sampson, “Therapeutic targeting of mTOR in tuberous sclerosis,” Biochemical Society Transactions, vol. 37, no. 1, pp. 259–264, 2009. View at Publisher · View at Google Scholar · View at PubMed
  49. C. Medeiros, M. J. Frederico, G. Da Luz et al., “Exercise training reduces insulin resistance and upregulates the mTOR/p70S6k pathway in cardiac muscle of diet-induced obesity rats,” Journal of Cellular Physiology, vol. 226, no. 3, pp. 666–674, 2011. View at Publisher · View at Google Scholar · View at PubMed
  50. S. M. Ali and D. M. Sabatini, “Structure of S6 kinase 1 determines whether raptor-mTOR or rictor-mTOR phosphorylates its hydrophobic motif site,” Journal of Biological Chemistry, vol. 280, no. 20, pp. 19445–19448, 2005. View at Publisher · View at Google Scholar · View at PubMed
  51. H. Nojima, C. Tokunaga, S. Eguchi et al., “The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif,” Journal of Biological Chemistry, vol. 278, no. 18, pp. 15461–15464, 2003. View at Publisher · View at Google Scholar · View at PubMed
  52. X. Song, Y. Kusakari, C. Y. Xiao et al., “mTOR attenuates the inflammatory response in cardiomyocytes and prevents cardiac dysfunction in pathological hypertrophy,” American Journal of Physiology, vol. 299, no. 6, pp. C1256–C1266, 2010. View at Publisher · View at Google Scholar · View at PubMed
  53. W. H. Shen, Z. Chen, S. Shi et al., “Cardiac restricted overexpression of kinase-dead mammalian target of rapamycin (mTOR) mutant impairs the mtor-mediated signaling and cardiac function,” Journal of Biological Chemistry, vol. 283, no. 20, pp. 13842–13849, 2008. View at Publisher · View at Google Scholar · View at PubMed
  54. 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, pp. 1073–1082, 2011. View at Google Scholar
  55. V. G. Athyros, E. N. Liberopoulos, D. P. Mikhailidis et al., “Association of drinking pattern and alcohol beverage type with the prevalence of metabolic syndrome, diabetes, coronary heart disease, stroke, and peripheral arterial disease in a Mediterranean cohort,” Angiology, vol. 58, no. 6, pp. 689–697, 2008. View at Publisher · View at Google Scholar · View at PubMed
  56. G. Schaller, S. Kretschmer, G. Gouya et al., “Alcohol acutely increases vascular reactivity together with insulin sensitivity in type 2 diabetic men,” Experimental and Clinical Endocrinology and Diabetes, vol. 118, no. 1, pp. 57–60, 2010. View at Publisher · View at Google Scholar · View at PubMed
  57. M. S. Player, A. G. Mainous, D. E. King, V. A. Diaz, and C. J. Everett, “Moderate alcohol intake is associated with decreased risk of insulin resistance among individuals with vitamin D insufficiency,” Nutrition, vol. 26, no. 1, pp. 100–105, 2010. View at Publisher · View at Google Scholar · View at PubMed
  58. T. C. Vary, C. J. Lynch, and C. H. Lang, “Effects of chronic alcohol consumption on regulation of myocardial protein synthesis,” American Journal of Physiology, vol. 281, no. 3, pp. H1242–H1251, 2001. View at Google Scholar
  59. T. C. Vary, G. Deiter, and R. Lantry, “Chronic alcohol feeding impairs mTOR(Ser2448) phosphorylation in rat hearts,” Alcoholism: Clinical and Experimental Research, vol. 32, no. 1, pp. 43–51, 2008. View at Publisher · View at Google Scholar · View at PubMed
  60. C. H. Lang, R. A. Frost, A. D. Summer, and T. C. Vary, “Molecular mechanisms responsible for alcohol-induced myopathy in skeletal muscle and heart,” International Journal of Biochemistry and Cell Biology, vol. 37, no. 10, pp. 2180–2195, 2005. View at Publisher · View at Google Scholar · View at PubMed
  61. K. Inoki, Y. Li, T. Zhu, J. Wu, and K. L. Guan, “TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling,” Nature Cell Biology, vol. 4, no. 9, pp. 648–657, 2002. View at Publisher · View at Google Scholar · View at PubMed
  62. Y. Sancak, L. Bar-Peled, R. Zoncu, A. L. Markhard, S. Nada, and D. M. Sabatini, “Ragulator-rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids,” Cell, vol. 141, no. 2, pp. 290–303, 2010. View at Publisher · View at Google Scholar · View at PubMed
  63. M. D. Dennis, J. I. Baum, S. R. Kimball, and L. S. Jefferson, “Mechanisms involved in the coordinate regulation of mTORC1 by insulin and amino acids,” The Journal of Biological Chemistry, vol. 286, pp. 8287–8296, 2011. View at Google Scholar
  64. R. D. Hannan, A. Jenkins, A. K. Jenkins, and Y. Brandenburger, “Cardiac hypertrophy: a matter of translation,” Clinical and Experimental Pharmacology and Physiology, vol. 30, no. 8, pp. 517–527, 2003. View at Publisher · View at Google Scholar
  65. B. D. Manning, “Balancing Akt with S6K: implications for both metabolic diseases and tumorigenesis,” Journal of Cell Biology, vol. 167, no. 3, pp. 399–403, 2004. View at Publisher · View at Google Scholar · View at PubMed
  66. 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. 8, pp. 2805–2816, 2010. View at Publisher · View at Google Scholar · View at PubMed
  67. X. Zhou, L. Ma, J. Habibi et al., “Nebivolol improves diastolic dysfunction and myocardial remodeling through reductions in oxidative stress in the zucker obese rat,” Hypertension, vol. 55, no. 4, pp. 880–888, 2010. View at Publisher · View at Google Scholar · View at PubMed
  68. J. C. Frisbee, “Hypertension-independent microvascular rarefaction in the obese Zucker rat model of the metabolic syndrome,” Microcirculation, vol. 12, no. 5, pp. 383–392, 2005. View at Publisher · View at Google Scholar · View at PubMed
  69. J. Ren, L. Pulakat, A. Whaley-Connell, and J. R. Sowers, “Mitochondrial biogenesis in the metabolic syndrome and cardiovascular disease,” Journal of Molecular Medicine, vol. 88, no. 10, pp. 993–1001, 2010. View at Publisher · View at Google Scholar · View at PubMed
  70. S. E. Alvarez, L. R. Seguin, R. S. Villarreal, C. Nahmias, and G. M. Ciuffo, “Involvement of c-Src tyrosine kinase in SHP-1 phosphatase activation by Ang II AT2 receptors in rat fetal tissues,” Journal of Cellular Biochemistry, vol. 105, no. 3, pp. 703–711, 2008. View at Publisher · View at Google Scholar · View at PubMed
  71. Y. Kambayashi, K. Nagata, T. Ichiki, and T. Inagami, “Insulin and insulin-like growth factors induce expression of angiotensin type-2 receptor in vascular-smooth-muscle cells,” European Journal of Biochemistry, vol. 239, no. 3, pp. 558–565, 1996. View at Google Scholar
  72. A. M. Samuelsson, E. Bollano, R. Mobini et al., “Hyperinsulinemia: effect on cardiac mass/function, angiotensin II receptor expression, and insulin signaling pathways,” American Journal of Physiology, vol. 291, no. 2, pp. H787–H796, 2006. View at Publisher · View at Google Scholar · View at PubMed
  73. G. W. Booz, “Putting the brakes on cardiac hypertrophy: exploiting the NO-cGMP counter-regulatory system,” Hypertension, vol. 45, no. 3, pp. 341–346, 2005. View at Publisher · View at Google Scholar · View at PubMed
  74. S. Bosnyak, I. K. Welungoda, A. Hallberg, M. Alterman, R. E. Widdop, and E. S. Jones, “Stimulation of angiotensin AT2 receptors by the non-peptide agonist, Compound 21, evokes vasodepressor effects in conscious spontaneously hypertensive rats,” British Journal of Pharmacology, vol. 159, no. 3, pp. 709–716, 2010. View at Publisher · View at Google Scholar · View at PubMed
  75. C. M. Bove, W. D. Gilson, C. D. Scott et al., “The angiotensin II type 2 receptor and improved adjacent region function post-MI,” Journal of Cardiovascular Magnetic Resonance, vol. 7, no. 2, pp. 459–464, 2005. View at Publisher · View at Google Scholar
  76. Z. Lako-Futo, I. Szokodi, B. Sarman et al., “Evidence for a functional role of angiotensin II type 2 receptor in the cardiac hypertrophic process in vivo in the rat heart,” Circulation, vol. 108, pp. 2414–2422, 2003. View at Google Scholar
  77. U. M. Steckelings, R. E. Widdop, L. Paulis, and T. Unger, “The angiotensin AT2 receptor in left ventricular hypertrophy,” Journal of Hypertension, vol. 28, no. 1, pp. S50–S55, 2010. View at Publisher · View at Google Scholar · View at PubMed
  78. B. Molavi, J. Chen, and J. L. Mehta, “Cardioprotective effects of rosiglitazone are associated with selective overexpression of type 2 angiotensin receptors and inhibition of p42/44 MAPK,” American Journal of Physiology, vol. 291, no. 2, pp. H687–H693, 2006. View at Publisher · View at Google Scholar · View at PubMed
  79. C. A. M. Van Kesteren, H. A. A. Van Heugten, J. M. J. Lamers, P. R. Saxena, M. A. D. H. Schalekamp, and A. H. J. Danser, “Angiotensin II-mediated growth and antigrowth effects in cultured neonatal rat cardiac myocytes and fibroblasts,” Journal of Molecular and Cellular Cardiology, vol. 29, no. 8, pp. 2147–2157, 1997. View at Publisher · View at Google Scholar · View at PubMed
  80. X. Yan, A. J. T. Schuldt, R. L. Price et al., “Pressure overload-induced hypertrophy in transgenic mice selectively overexpressing AT2 receptors in ventricular myocytes,” American Journal of Physiology, vol. 294, no. 3, pp. H1274–H1281, 2008. View at Publisher · View at Google Scholar · View at PubMed
  81. D. Ferland-McCollough, S. E. Ozanne, K. Siddle, A. E. Willisand, and M. Bushell, “The involvement of microRNAs in type 2 diabetes,” Biochemical Society Transactions, vol. 38, no. 6, pp. 1565–1570, 2010. View at Publisher · View at Google Scholar · View at PubMed
  82. S. Qin and C. Zhang, “MicroRNAs in vascular disease,” Journal of Cardiovascular Pharmacology, vol. 57, pp. 8–12, 2011. View at Google Scholar
  83. R. J. A. Frost and E. Van Rooij, “miRNAs as therapeutic targets in ischemic heart disease,” Journal of Cardiovascular Translational Research, vol. 3, no. 3, pp. 280–289, 2010. View at Publisher · View at Google Scholar · View at PubMed
  84. J. K. Edwards, R. Pasqualini, W. Arap, and G. A. Calin, “MicroRNAs and ultraconserved genes as diagnostic markers and therapeutic targets in cancer and cardiovascular diseases,” Journal of Cardiovascular Translational Research, vol. 3, no. 3, pp. 271–279, 2010. View at Publisher · View at Google Scholar · View at PubMed
  85. E. van Rooij, D. Quiat, B. A. Johnson et al., “A Family of microRNAs Encoded by Myosin Genes Governs Myosin Expression and Muscle Performance,” Developmental Cell, vol. 17, no. 5, pp. 662–673, 2009. View at Publisher · View at Google Scholar · View at PubMed
  86. T. E. Callis, K. Pandya, Y. S. Hee et al., “MicroRNA-208a is a regulator of cardiac hypertrophy and conduction in mice,” Journal of Clinical Investigation, vol. 119, no. 9, pp. 2772–2786, 2009. View at Publisher · View at Google Scholar · View at PubMed
  87. E. Van Rooij, L. B. Sutherland, X. Qi, J. A. Richardson, J. Hill, and E. N. Olson, “Control of stress-dependent cardiac growth and gene expression by a microRNA,” Science, vol. 316, no. 5824, pp. 575–579, 2007. View at Publisher · View at Google Scholar · View at PubMed
  88. G. Condorelli, M. V. G. Latronico, and G. W. Dorn, “MicroRNAs in heart disease: putative novel therapeutic targets?” European Heart Journal, vol. 31, no. 6, pp. 649–658, 2010. View at Publisher · View at Google Scholar · View at PubMed
  89. H. Naraba and N. Iwai, “Assessment of the MicroRNA system in salt-sensitive hypertension,” Hypertension Research, vol. 28, no. 10, pp. 819–826, 2005. View at Google Scholar
  90. G. K. Wang, J. Q. Zhu, J. T. Zhang et al., “Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans,” European Heart Journal, vol. 31, no. 6, pp. 659–666, 2010. View at Publisher · View at Google Scholar · View at PubMed
  91. X. Ji, R. Takahashi, Y. Hiura, G. Hirokawa, Y. Fukushima, and N. Iwai, “Plasma miR-208 as a biomarker of myocardial injury,” Clinical Chemistry, vol. 55, no. 11, pp. 1944–1949, 2009. View at Publisher · View at Google Scholar · View at PubMed
  92. A. J. Tijsen, E. E. Creemers, P. D. Moerland et al., “MiR423-5p as a circulating biomarker for heart failure,” Circulation Research, vol. 106, no. 6, pp. 1035–1039, 2010. View at Publisher · View at Google Scholar · View at PubMed
  93. S. D. Jordan, M. Krüger, D. M. Willmes et al., “Obesity-induced overexpression of miRNA-143 inhibits insulin-stimulated AKT activation and impairs glucose metabolism,” Nature Cell Biology, vol. 13, pp. 434–446, 2011. View at Google Scholar
  94. S. H. Um, F. Frigerio, M. Watanabe et al., “Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity,” Nature, vol. 431, no. 7005, pp. 200–205, 2004. View at Publisher · View at Google Scholar · View at PubMed
  95. H. Y. Huang, C. H. Chien, K. H. Jen, and H. D. Huang, “RegRNA: an integrated web server for identifying regulatory RNA motifs and elements,” Nucleic Acids Research, vol. 34, pp. W429–W434, 2006. View at Publisher · View at Google Scholar · View at PubMed
  96. Affymetrix Data sheet GeneChip miRNA Array.
  97. R. Schickel, S. M. Park, A. E. Murmann, and M. E. Peter, “miR-200c regulates induction of apoptosis through CD95 by targeting FAP-1,” Molecular cell, vol. 38, no. 6, pp. 908–915, 2010. View at Google Scholar
  98. U. Wellner, J. Schubert, U. C. Burk et al., “The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs.,” Nature cell biology, vol. 11, no. 12, pp. 1487–1495, 2009. View at Google Scholar
  99. C. D. Spies, M. Sander, K. Stangl et al., “Effects of alcohol on the heart,” Current Opinion in Critical Care, vol. 7, no. 5, pp. 337–343, 2001. View at Publisher · View at Google Scholar
  100. W. K. Jones, “A murine model of alcoholic cardiomyopathy A role for zinc and metallotheienin in fibrosis,” American Journal of Pathology, vol. 167, pp. 301–304, 2005. View at Google Scholar
  101. M. R. Piano, “Alcoholic cardiomyopathy: incidence, clinical characteristics, and pathophysiology,” Chest, vol. 121, no. 5, pp. 1638–1650, 2002. View at Publisher · View at Google Scholar
  102. J. Ren and L. E. Wold, “Mechanisms of alcoholic heart disease,” Therapeutic Advances in Cardiovascular Disease, vol. 2, no. 6, pp. 497–506, 2008. View at Publisher · View at Google Scholar · View at PubMed
  103. R. A. Kloner and S. H. Rezkalla, “To drink or not to drink? That is the question,” Circulation, vol. 116, no. 11, pp. 1306–1317, 2007. View at Publisher · View at Google Scholar · View at PubMed
  104. WHO, 2008–2013 Action Plan for Global Strategy for the Prevention and Control of Noncommunicable Diseases, World Health Organization, Geneva, Switzerland, 2008.
  105. J. W. Ting and W. W. Lautt, “The effects of acute, chronic and prenatal exposure on inulin sensitivity,” Pharmacology & Therapeutics, vol. 11, pp. 346–373, 2006. View at Google Scholar
  106. D. L. Lucas, R. A. Brown, M. Wassef, and T. D. Giles, “Alcohol and the cardiovascular system: research challenges and opportunities,” Journal of the American College of Cardiology, vol. 45, no. 12, pp. 1916–1924, 2005. View at Publisher · View at Google Scholar · View at PubMed
  107. M. Vernary, B. Balkau, J. G. Moreau, J. Sigalas, M. C. Chesnier, and P. Ducimeteriere, “Alcohol consumption and insulin resistance syndrome parameters.: associations and evolutions in a longitudinal analysis of the French DESIR cohort,” Annals of Epidemiology, vol. 14, pp. 209–214, 2004. View at Google Scholar
  108. A. Z. Fan, M. Russell, T. Naimi et al., “Patterns of alcohol consumption and the metabolic syndrome,” The Journal of Clinical Endocrinology & Metabolism, vol. 93, pp. 3833–3838, 2008. View at Google Scholar
  109. T. Limin, X. Hou, J. Liu et al., “Chronic ethanol consumption resulting in the downregulation of insulin receptor-β subunit, insulin receptor substrate-1, and glucose transporter 4 expression in rat cardiac muscles,” Alcohol, vol. 43, no. 1, pp. 51–58, 2009. View at Publisher · View at Google Scholar · View at PubMed
  110. S. Y. Li and J. Ren, “Cardiac overexpression of alcohol dehydrogenase exacerbates chronic ethanol ingestion-induced myocardial dysfunction and hypertrophy: role of insulin signaling and ER stress,” Journal of Molecular and Cellular Cardiology, vol. 44, no. 6, pp. 992–1001, 2008. View at Publisher · View at Google Scholar · View at PubMed
  111. S. Y. Li, S. A. B. Gilbert, Q. Li, and J. Ren, “Aldehyde dehydrogenase-2 (ALDH2) ameliorates chronic alcohol ingestion-induced myocardial insulin resistance and endoplasmic reticulum stress,” Journal of Molecular and Cellular Cardiology, vol. 47, no. 2, pp. 247–255, 2009. View at Publisher · View at Google Scholar · View at PubMed
  112. Q. Li and J. Ren, “Chronic alcohol consumption alters mammalian target of rapamycin (mTOR), reduces ribosomal p70s6 kinase and p4E-BP1 levels in mouse cerebral cortex,” Experimental Neurology, vol. 204, no. 2, pp. 840–844, 2007. View at Publisher · View at Google Scholar · View at PubMed
  113. B. K. Elamin, E. Callegari, L. Gramantieri, S. Sabbioni, and M. Negrini, “MicroRNA response to environmental mutagens in liver,” Mutation Research. In press.
  114. A. Dolganiuc, J. Petrasek, K. Kodys et al., “MicroRNA expression profile in lieber-decarli diet-induced alcoholic and methionine choline deficient diet-induced nonalcoholic steatohepatitis models in mice,” Alcoholism: Clinical and Experimental Research, vol. 33, no. 10, pp. 1704–1710, 2009. View at Publisher · View at Google Scholar · View at PubMed
  115. Y. Tang, A. Banan, C. B. Forsyth et al., “Effect of alcohol on miR-212 expression in intestinal epithelial cells and its potential role in alcoholic liver disease,” Alcoholism: Clinical and Experimental Research, vol. 32, no. 2, pp. 355–364, 2008. View at Publisher · View at Google Scholar · View at PubMed
  116. N. Wang, Z. Zhou, X. Liao, and T. Zhang, “Role of microRNAs in cardiac hypertrophy and heart failure,” IUBMB Life, vol. 61, no. 6, pp. 566–571, 2009. View at Publisher · View at Google Scholar · View at PubMed
  117. T. Thum, P. Galuppo, C. Wolf et al., “MicroRNAs in the human heart: a clue to fetal gene reprogramming in heart failure,” Circulation, vol. 116, no. 3, pp. 258–267, 2007. View at Publisher · View at Google Scholar · View at PubMed
  118. G. B. Collins, K. B. Brosnihan, R. A. Zuti, M. Messina, and M. K. Gupta, “Neuroendocrine, fluid balance, and thirst responses to alcohol in alcoholics,” Alcoholism: Clinical and Experimental Research, vol. 16, no. 2, pp. 228–233, 1992. View at Publisher · View at Google Scholar
  119. C. P. Cheng, H. J. Cheng, C. Cunningham et al., “Angiotensin II type 1 receptor blockade prevents alcoholic cardiomyopathy,” Circulation, vol. 114, no. 3, pp. 226–236, 2006. View at Publisher · View at Google Scholar · View at PubMed
  120. L. Jing, W. M. Li, L. J. Zhou, S. Li, J. J. Kou, and J. Song, “Expression of renin-angiotensin system and peroxisome proliferator- activated receptors in alcoholic cardiomyopathy,” Alcoholism: Clinical and Experimental Research, vol. 32, no. 11, pp. 1999–2007, 2008. View at Publisher · View at Google Scholar · View at PubMed
  121. J. Fernández-Solà, J. M. Nicolás, J. Oriola et al., “Angiotensin-converting enzyme gene polymorphism is associated with vulnerability to alcoholic cardiomyopathy,” Annals of Internal Medicine, vol. 137, no. 5 I, pp. 321–326, 2002. View at Google Scholar
  122. A. R. Aroor and S. D. Shukla, “MAP kinase signaling in diverse effects of ethanol,” Life Sciences, vol. 74, no. 19, pp. 2339–2364, 2004. View at Publisher · View at Google Scholar
  123. Y. Izawa, M. Yoshizumi, Y. Fujita et al., “ERK1/2 activation by angiotensin II inhibits insulin-induced glucose uptake in vascular smooth muscle cells,” Experimental Cell Research, vol. 308, no. 2, pp. 291–299, 2005. View at Publisher · View at Google Scholar · View at PubMed
  124. C. Alfarano, L. Sartiani, C. Nidiani et al., “Functional coupling of angiotensin II type 1 receptor with insulin resistance of energy substrate uptakes in immortalized cardiomyocytes (HL-1 cells),” British Journal of Pharmacology, vol. 153, pp. 907–914, 2008. View at Google Scholar
  125. P. L. Jeppesen, G. L. Christensen, M. Schneider et al., “Angiotensin II type 1 receptor signalling regulates microRNA differentially in cardiac fibroblasts andmyocytes,” British Journal of Pharmacology, vol. 164, no. 2, pp. 394–404, 2011. View at Google Scholar
  126. T. A. Doser, S. Turdi, D. P. Thomas, P. N. Epstein, S. Y. Li, and J. Ren, “Transgenic overexpression of aldehyde dehydrogenase-2 rescues chronic alcohol intake-induced myocardial hypertrophy and contractile dysfunction,” Circulation, vol. 119, no. 14, pp. 1941–1949, 2009. View at Publisher · View at Google Scholar · View at PubMed
  127. J. Remenyi, C. J. Hunter, C. Cole et al., “Regulation of the miR-212/132 locus by MSK1 and CREB in response to neurotrophins,” Biochemical Journal, vol. 428, no. 2, pp. 281–291, 2010. View at Publisher · View at Google Scholar · View at PubMed
  128. S. Y. Li, Q. Li, J. J. Shen et al., “Attenuation of acetaldehyde-induced cell injury by overexpression of aldehyde dehydrogenase-2 (ALDH2) transgene in human cardiac myocytes: role of MAP kinase signaling,” Journal of Molecular and Cellular Cardiology, vol. 40, no. 2, pp. 283–294, 2006. View at Publisher · View at Google Scholar · View at PubMed
  129. Z. Paroo, X. Ye, S. Chen, and Q. Liu, “Phosphorylation of the human microRNA-generating complex mediates MAPK/Erk signaling,” Cell, vol. 139, no. 1, pp. 112–122, 2009. View at Publisher · View at Google Scholar · View at PubMed
  130. S. J. Buss, J. H. Riffel, H. A. Katus, and S. E. Hardt, “Augmentation of autophagy by mTOR-inhibition in myocardial infarction: when size matters,” Autophagy, vol. 6, no. 2, pp. 304–306, 2010. View at Publisher · View at Google Scholar
  131. 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 PubMed
  132. S. J. Buss, S. Muenz, J. H. Riffel et al., “Beneficial effects of mammalian target of rapamycin inhibition on left ventricular remodeling after myocardial infarction,” Journal of the American College of Cardiology, vol. 54, no. 25, pp. 2435–2446, 2009. View at Publisher · View at Google Scholar · View at PubMed
  133. W. Ge and J. Ren, “mTOR-STAT3-notch signaling contributes to ALDH2-induced protection against cardiac contractile dysfunction and autophagy under alcoholism,” Journal of Cellular and Molecular Medicine. In press.
  134. Y. Zhang and J. Ren, “ALDH2 in alcoholic heart diseases: molecular mechanism and clinical implications,” Pharmacology & Therapeutics, vol. 132, no. 1, pp. 86–95, 2011. View at Google Scholar
  135. S. V. Penumathsa, M. Thirunavukkarasu, L. Zhan et al., “Resveratrol enhances GLUT-4 translocation to the caveolar lipid raft fractions through AMPK/Akt/eNOS signalling pathway in diabetic myocardium,” Journal of Cellular and Molecular Medicine, vol. 12, no. 6A, pp. 2350–2361, 2008. View at Publisher · View at Google Scholar · View at PubMed
  136. S. V. Penumathsa, M. Thirunavukkarasu, S. M. Samuel et al., “Niacin bound chromium treatment induces myocardial Glut-4 translocation and caveolar interaction via Akt, AMPK and eNOS phosphorylation in streptozotocin induced diabetic rats after ischemia-reperfusion injury,” Biochimica et Biophysica Acta, vol. 1792, pp. 39–48, 2009. View at Google Scholar
  137. R. R. Russell, R. Bergeron, G. I. Shulman, and L. H. Young, “Translocation of myocardial GLUT-4 and increased glucose uptake through activation of AMPK by AICAR,” American Journal of Physiology, vol. 277, no. 2, pp. H643–H649, 1999. View at Google Scholar
  138. L. Y. Chen, F. R. Wang, X. L. Sun et al., “Chronic ethanol feeding impairs AMPK and MEF2 expression and is associated with GLUT4 decrease in rat myocardium,” Experimental and Molecular Medicine, vol. 42, no. 3, pp. 205–215, 2010. View at Publisher · View at Google Scholar
  139. B. D. Brown and L. Naldini, “Exploiting and antagonizing microRNA regulation for therapeutic and experimental applications,” Nature Reviews Genetics, vol. 10, no. 8, pp. 578–585, 2009. View at Publisher · View at Google Scholar · View at PubMed
  140. J. A. Broderick and P. D. Zamore, “MicroRNA therapeutics,” Gene Therapy. In press.
  141. D. Sayed and M. Abdellatif, “MicroRNAs in development and disease,” Physiological Reviews, vol. 91, no. 3, pp. 827–887, 2011. View at Google Scholar
  142. C. Esau, S. Davis, S. F. Murray et al., “miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting,” Cell Metabolism, vol. 3, no. 2, pp. 87–98, 2006. View at Publisher · View at Google Scholar · View at PubMed
  143. J. Krützfeldt, N. Rajewsky, R. Braich et al., “Silencing of microRNAs in vivo with 'antagomirs',” Nature, vol. 438, no. 7068, pp. 685–689, 2005. View at Publisher · View at Google Scholar · View at PubMed
  144. T. Thum, C. Gross, J. Fiedler et al., “MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts,” Nature, vol. 456, no. 7224, pp. 980–984, 2008. View at Publisher · View at Google Scholar · View at PubMed
  145. M. S. Ebert, J. R. Neilson, and P. A. Sharp, “MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells,” Nature Methods, vol. 4, no. 9, pp. 721–726, 2007. View at Publisher · View at Google Scholar · View at PubMed
  146. D. Sayed, S. Rane, J. Lypowy et al., “MicroRNA-21 targets Sprouty2 and promotes cellular outgrowths,” Molecular Biology of the Cell, vol. 19, no. 8, pp. 3272–3282, 2008. View at Publisher · View at Google Scholar · View at PubMed
  147. S. Oba, S. Kumano, E. Suzuki et al., “miR-200b precursor can ameliorate renal tubulointerstitial fibrosis,” PLoS ONE, vol. 5, no. 10, Article ID e13614, 2010. View at Publisher · View at Google Scholar · View at PubMed