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Current Heart Failure Reports

, Volume 9, Issue 3, pp 164–173 | Cite as

AMP-activated Protein Kinase in the Control of Cardiac Metabolism and Remodeling

  • Sandrine Horman
  • Christophe Beauloye
  • Jean-Louis Vanoverschelde
  • Luc BertrandEmail author
Investigative Therapies (J.-L. Balligand, Section editor)

Abstract

The AMP-activated protein kinase (AMPK) can be firstly considered as a cellular fuel gauge. AMPK rapidly senses energy deprivation and orchestrates a metabolic response to maintain an acceptable energy level required for cell survival under such adverse condition. Its protective role during myocardial ischemia has been deeply documented. More recently, it has been shown that the role of AMPK extends to several nonmetabolic effects related to other cardiac pathologies comprising diabetic cardiomyopathy, cardiac hypertrophy, and heart failure. Here, we briefly review the different roles played by AMPK in the control of cardiac metabolism and function under normal and pathological conditions. The potential cardioprotective actions of AMPK and the relative importance of its energetic and nonmetabolic effects in these mechanisms are deeply discussed.

Keywords

AMP-activated protein kinase AMPK Angiogenesis Cardiac remodeling Diabetic cardiomyopathy Energy sensor Extracellular matrix Fibrosis Heart failure Hypertrophy Insulin resistance Metabolism Myocardial infarction Myocardial ischemia Protein synthesis 

Notes

Acknowledgments

The authors are supported by the Fonds National de la Recherche Scientifique et Médicale (Belgium) and the Actions de Recherche Concertées (Belgium). Dr. Sandrine Horman and Dr. Luc Bertrand are Research Associates of the Fonds National de la Recherche Scientifique, Belgium.

Disclosures

No potential conflicts of interest relevant to this article were reported.

References

Papers of particular interest, published recently, have been highlighted as: •Of importance ••Of major importance

  1. 1.
    Viollet B, Athea Y, Mounier R, et al. AMPK: Lessons from transgenic and knockout animals. Front Biosci. 2009;14:19–44.PubMedCrossRefGoogle Scholar
  2. 2.
    Sakamoto K, Zarrinpashneh E, Budas GR, et al. Deficiency of LKB1 in heart prevents ischemia-mediated activation of AMPKalpha2 but not AMPKalpha1. Am J Physiol Endocrinol Metab. 2006;290:E780–8.PubMedCrossRefGoogle Scholar
  3. 3.
    Woods A, Dickerson K, Heath R, et al. Ca2+/calmodulin-dependent protein kinase kinase-beta acts upstream of AMP-activated protein kinase in mammalian cells. Cell Metab. 2005;2:21–33.PubMedCrossRefGoogle Scholar
  4. 4.
    Hawley SA, Pan DA, Mustard KJ, et al. Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase. Cell Metab. 2005;2:9–19.PubMedCrossRefGoogle Scholar
  5. 5.
    Beauloye C, Bertrand L, Horman S, et al. AMPK activation, a preventive therapeutic target in the transition from cardiac injury to heart failure. Cardiovasc Res. 2011;90:224–33.PubMedCrossRefGoogle Scholar
  6. 6.
    Neubauer S. The failing heart–an engine out of fuel. N Engl J Med. 2007;356:1140–51.PubMedCrossRefGoogle Scholar
  7. 7.
    Bertrand L, Horman S, Beauloye C, et al. Insulin signalling in the heart. Cardiovasc Res. 2008;79:238–48.PubMedCrossRefGoogle Scholar
  8. 8.
    Treebak JT, Glund S, Deshmukh A, et al. AMPK-mediated AS160 phosphorylation in skeletal muscle is dependent on AMPK catalytic and regulatory subunits. Diabetes. 2006;55:2051–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Kramer HF, Witczak CA, Fujii N, et al. Distinct signals regulate AS160 phosphorylation in response to insulin, AICAR, and contraction in mouse skeletal muscle. Diabetes. 2006;55:2067–76.PubMedCrossRefGoogle Scholar
  10. 10.
    Marsin AS, Bertrand L, Rider MH, et al. Phosphorylation and activation of heart PFK-2 by AMPK has a role in the stimulation of glycolysis during ischaemia. Curr Biol. 2000;10:1247–55.PubMedCrossRefGoogle Scholar
  11. 11.
    Kudo N, Gillespie JG, Kung L, et al. Characterization of 5′AMP-activated protein kinase activity in the heart and its role in inhibiting acetyl-CoA carboxylase during reperfusion following ischemia. Biochim Biophys Acta. 1996;1301:67–75.PubMedCrossRefGoogle Scholar
  12. 12.
    Dyck JR, Lopaschuk GD. AMPK alterations in cardiac physiology and pathology: enemy or ally? J Physiol. 2006;574:95–112.PubMedCrossRefGoogle Scholar
  13. 13.
    Zarrinpashneh E, Carjaval K, Beauloye C, et al. Role of the alpha2-isoform of AMP-activated protein kinase in the metabolic response of the heart to no-flow ischemia. Am J Physiol Heart Circ Physiol. 2006;291:H2875–83.PubMedCrossRefGoogle Scholar
  14. 14.
    Carvajal K, Zarrinpashneh E, Szarszoi O, et al. Dual cardiac contractile effects of the alpha2-AMPK deletion in low-flow ischemia and reperfusion. Am J Physiol Heart Circ Physiol. 2007;292:H3136–47.PubMedCrossRefGoogle Scholar
  15. 15.
    Russell 3rd RR, Li J, Coven DL, et al. AMP-activated protein kinase mediates ischemic glucose uptake and prevents postischemic cardiac dysfunction, apoptosis, and injury. J Clin Invest. 2004;114:495–503.PubMedGoogle Scholar
  16. 16.
    •• Gundewar S, Calvert JW, Jha S, et al. Activation of AMP-activated protein kinase by metformin improves left ventricular function and survival in heart failure. Circ Res. 2009;104:403–11. This study demonstrates that low-dose metformin significantly improves left ventricular function and survival via activation of AMPK and its downstream mediators, eNOS and PGC-1alpha, in a model of heart failure. They used an AMPK dominant-negative mouse model to prove the implication of AMPK.PubMedCrossRefGoogle Scholar
  17. 17.
    • Kim AS, Miller EJ, Wright TM, et al. A small molecule AMPK activator protects the heart against ischemia-reperfusion injury. J Mol Cell Cardiol. 2011;51:24–32. The authors were the first to show that treatment with a direct AMPK-activating molecule, the A-769662, is an effective strategy to protect the heart against ischemia–reperfusion injury. They used an AMPK dominant-negative mouse model to prove the implication of AMPK.PubMedCrossRefGoogle Scholar
  18. 18.
    Calvert JW, Gundewar S, Jha S, et al. Acute metformin therapy confers cardioprotection against myocardial infarction via AMPK-eNOS-mediated signaling. Diabetes. 2008;57:696–705.PubMedCrossRefGoogle Scholar
  19. 19.
    Xing Y, Musi N, Fujii N, et al. Glucose metabolism and energy homeostasis in mouse hearts overexpressing dominant negative alpha2 subunit of AMP-activated protein kinase. J Biol Chem. 2003;278:28372–7.PubMedCrossRefGoogle Scholar
  20. 20.
    Boudina S, Abel ED. Diabetic cardiomyopathy, causes and effects. Rev Endocr Metab Disord. 2010;11:31–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Zhou G, Myers R, Li Y, et al. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest. 2001;108:1167–74.PubMedGoogle Scholar
  22. 22.
    Bertrand L, Ginion A, Beauloye C, et al. AMPK activation restores the stimulation of glucose uptake in an in vitro model of insulin-resistant cardiomyocytes via the activation of protein kinase B. Am J Physiol Heart Circ Physiol. 2006;291:H239–50.PubMedCrossRefGoogle Scholar
  23. 23.
    • Ginion A, Auquier J, Benton CR, et al. Inhibition of the mTOR/p70S6K pathway is not involved in the insulin-sensitizing effect of AMPK on cardiac glucose uptake. Am J Physiol Heart Circ Physiol. 2011;301:H469–77. In contrast to a commonly accepted notion, the authors showed that the insulin-sensitizing effect of AMPK on insulin-mediated glucose uptake is not due to the AMPK-induced inhibition of the mTOR/p70S6K-dependent negative feedback loop.PubMedCrossRefGoogle Scholar
  24. 24.
    Longnus SL, Segalen C, Giudicelli J, et al. Insulin signalling downstream of protein kinase B is potentiated by 5′AMP-activated protein kinase in rat hearts in vivo. Diabetologia. 2005;48:2591–601.PubMedCrossRefGoogle Scholar
  25. 25.
    Yang J, Holman GD. Long-term metformin treatment stimulates cardiomyocyte glucose transport through an AMP-activated protein kinase-dependent reduction in GLUT4 endocytosis. Endocrinology. 2006;147:2728–36.PubMedCrossRefGoogle Scholar
  26. 26.
    Tremblay F, Marette A. Amino acid and insulin signaling via the mTOR/p70 S6 kinase pathway. A negative feedback mechanism leading to insulin resistance in skeletal muscle cells. J Biol Chem. 2001;276:38052–60.PubMedGoogle Scholar
  27. 27.
    Boura-Halfon S, Zick Y. Phosphorylation of IRS proteins, insulin action, and insulin resistance. Am J Physiol Endocrinol Metab. 2009;296:E581–91.PubMedCrossRefGoogle Scholar
  28. 28.
    Habegger KM, Hoffman NJ, Ridenour CM, et al. AMPK enhances insulin-stimulated GLUT4 regulation via lowering membrane cholesterol. Endocrinology. 2012;153:2130–41.PubMedCrossRefGoogle Scholar
  29. 29.
    Xie Z, He C, Zou MH. AMP-activated protein kinase modulates cardiac autophagy in diabetic cardiomyopathy. Autophagy. 2011;7:1254–5.PubMedCrossRefGoogle Scholar
  30. 30.
    Matsumoto T, Noguchi E, Ishida K, et al. Metformin normalizes endothelial function by suppressing vasoconstrictor prostanoids in mesenteric arteries from OLETF rats, a model of type 2 diabetes. Am J Physiol Heart Circ Physiol. 2008;295:H1165–76.PubMedCrossRefGoogle Scholar
  31. 31.
    Wang Y, Huang Y, Lam KS, et al. Berberine prevents hyperglycemia-induced endothelial injury and enhances vasodilatation via adenosine monophosphate-activated protein kinase and endothelial nitric oxide synthase. Cardiovasc Res. 2009;82:484–92.PubMedCrossRefGoogle Scholar
  32. 32.
    Paiva MA, Rutter-Locher Z, Goncalves LM, et al. Enhancing AMPK activation during ischemia protects the diabetic heart against reperfusion injury. Am J Physiol Heart Circ Physiol. 2011;300:H2123–34.PubMedCrossRefGoogle Scholar
  33. 33.
    Krause U, Bertrand L, Hue L. Control of p70 ribosomal protein S6 kinase and acetyl-CoA carboxylase by AMP-activated protein kinase and protein phosphatases in isolated hepatocytes. Eur J Biochem. 2002;269:3751–9.PubMedCrossRefGoogle Scholar
  34. 34.
    Horman S, Browne G, Krause U, et al. Activation of AMP-activated protein kinase leads to the phosphorylation of elongation factor 2 and an inhibition of protein synthesis. Curr Biol. 2002;12:1419–23.PubMedCrossRefGoogle Scholar
  35. 35.
    Inoki K, Zhu T, Guan KL. TSC2 mediates cellular energy response to control cell growth and survival. Cell. 2003;115:577–90.PubMedCrossRefGoogle Scholar
  36. 36.
    Gwinn DM, Shackelford DB, Egan DF, et al. AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell. 2008;30:214–26.PubMedCrossRefGoogle Scholar
  37. 37.
    Browne GJ, Finn SG, Proud CG. Stimulation of the AMP-activated protein kinase leads to activation of eukaryotic elongation factor 2 kinase and to its phosphorylation at a novel site, serine 398. J Biol Chem. 2004;279:12220–31.PubMedCrossRefGoogle Scholar
  38. 38.
    Horman S, Beauloye C, Vertommen D, et al. Myocardial ischemia and increased heart work modulate the phosphorylation state of eukaryotic elongation factor-2. J Biol Chem. 2003;278:41970–6.PubMedCrossRefGoogle Scholar
  39. 39.
    Crozier SJ, Vary TC, Kimball SR, et al. Cellular energy status modulates translational control mechanisms in ischemic-reperfused rat hearts. Am J Physiol Heart Circ Physiol. 2005;289:H1242–50.PubMedCrossRefGoogle Scholar
  40. 40.
    Chan AY, Soltys CL, Young ME, et al. Activation of AMP-activated protein kinase inhibits protein synthesis associated with hypertrophy in the cardiac myocyte. J Biol Chem. 2004;279:32771–9.PubMedCrossRefGoogle Scholar
  41. 41.
    Chan AY, Dolinsky VW, Soltys CL, et al. Resveratrol inhibits cardiac hypertrophy via AMP-activated protein kinase and Akt. J Biol Chem. 2008;283:24194–201.PubMedCrossRefGoogle Scholar
  42. 42.
    • Dolinsky VW, Morton JS, Oka T, et al. Calorie restriction prevents hypertension and cardiac hypertrophy in the spontaneously hypertensive rat. Hypertension. 2010;56:412–21. The authors showed that short-term calorie restriction exerts beneficial effects in hypertensive rats via stimulation of an adiponectin/AMPK/eNOS signaling axis. PubMedCrossRefGoogle Scholar
  43. 43.
    Zarrinpashneh E, Beauloye C, Ginion A, et al. AMPKalpha2 counteracts the development of cardiac hypertrophy induced by isoproterenol. Biochem Biophys Res Commun. 2008;376:677–81.PubMedCrossRefGoogle Scholar
  44. 44.
    Zhang P, Hu X, Xu X, et al. AMP activated protein kinase-alpha2 deficiency exacerbates pressure-overload-induced left ventricular hypertrophy and dysfunction in mice. Hypertension. 2008;52:918–24.PubMedCrossRefGoogle Scholar
  45. 45.
    • Shimano M, Ouchi N, Shibata R, et al. Adiponectin deficiency exacerbates cardiac dysfunction following pressure overload through disruption of an AMPK-dependent angiogenic response. J Mol Cell Cardiol. 2010;49:210–20. The authors showed that adiponectin deficiency accelerates the transition from cardiac hypertrophy to heart failure during pressure overload through disruption of AMPK-dependent angiogenic regulatory axis.PubMedCrossRefGoogle Scholar
  46. 46.
    Ikeda Y, Sato K, Pimentel DR, et al. Cardiac-specific deletion of LKB1 leads to hypertrophy and dysfunction. J Biol Chem. 2009;284:35839–49.PubMedCrossRefGoogle Scholar
  47. 47.
    Meng R, Pei Z, Zhang A, et al. AMPK activation enhances PPARalpha activity to inhibit cardiac hypertrophy via ERK1/2 MAPK signaling pathway. Arch Biochem Biophys. 2011;511:1–7.PubMedCrossRefGoogle Scholar
  48. 48.
    Li HL, Yin R, Chen D, et al. Long-term activation of adenosine monophosphate-activated protein kinase attenuates pressure-overload-induced cardiac hypertrophy. J Cell Biochem. 2007;100:1086–99.PubMedCrossRefGoogle Scholar
  49. 49.
    Chen BL, Ma YD, Meng RS, et al. Activation of AMPK inhibits cardiomyocyte hypertrophy by modulating of the FOXO1/MuRF1 signaling pathway in vitro. Acta Pharmacol Sin. 2010;31:798–804.PubMedCrossRefGoogle Scholar
  50. 50.
    Meng RS, Pei ZH, Yin R, et al. Adenosine monophosphate-activated protein kinase inhibits cardiac hypertrophy through reactivating peroxisome proliferator-activated receptor-alpha signaling pathway. Eur J Pharmacol. 2009;620:63–70.PubMedCrossRefGoogle Scholar
  51. 51.
    Opie LH, Commerford PJ, Gersh BJ, et al. Controversies in ventricular remodelling. Lancet. 2006;367:356–67.PubMedCrossRefGoogle Scholar
  52. 52.
    Knoll R, Iaccarino G, Tarone G, et al. Towards a re-definition of ‘cardiac hypertrophy’ through a rational characterization of left ventricular phenotypes: a position paper of the Working Group ‘Myocardial Function’ of the ESC. Eur J Heart Fail. 2011;13:811–9.PubMedCrossRefGoogle Scholar
  53. 53.
    Frey N, Olson EN. Cardiac hypertrophy: the good, the bad, and the ugly. Annu Rev Physiol. 2003;65:45–79.PubMedCrossRefGoogle Scholar
  54. 54.
    Baudino TA, Carver W, Giles W, et al. Cardiac fibroblasts: friend or foe? Am J Physiol Heart Circ Physiol. 2006;291:H1015–26.PubMedCrossRefGoogle Scholar
  55. 55.
    Eckhouse SR, Spinale FG. Changes in the myocardial interstitium and contribution to the progression of heart failure. Heart Fail Clin. 2012;8:7–20.PubMedCrossRefGoogle Scholar
  56. 56.
    Takeda N, Manabe I, Uchino Y, et al. Cardiac fibroblasts are essential for the adaptive response of the murine heart to pressure overload. J Clin Invest. 2010;120:254–65.PubMedCrossRefGoogle Scholar
  57. 57.
    Bishop SP, Powell PC, Hasebe N, et al. Coronary vascular morphology in pressure-overload left ventricular hypertrophy. J Mol Cell Cardiol. 1996;28:141–54.PubMedCrossRefGoogle Scholar
  58. 58.
    Balligand JL, Feron O, Dessy C. eNOS activation by physical forces: from short-term regulation of contraction to chronic remodeling of cardiovascular tissues. Physiol Rev. 2009;89:481–534.PubMedCrossRefGoogle Scholar
  59. 59.
    Spinale FG. Myocardial matrix remodeling and the matrix metalloproteinases: influence on cardiac form and function. Physiol Rev. 2007;87:1285–342.PubMedCrossRefGoogle Scholar
  60. 60.
    Banerjee I, Fuseler JW, Price RL, et al. Determination of cell types and numbers during cardiac development in the neonatal and adult rat and mouse. Am J Physiol Heart Circ Physiol. 2007;293:H1883–91.PubMedCrossRefGoogle Scholar
  61. 61.
    Sugihara N, Genda A, Shimizu M, et al. Diastolic dysfunction and its relation to myocardial fibrosis in essential hypertension. J Cardiol. 1988;18:353–61.PubMedGoogle Scholar
  62. 62.
    Bian ZY, Wei X, Deng S, et al.: Disruption of mindin exacerbates cardiac hypertrophy and fibrosis. J Mol Med (Berl) 2012. doi: 10.1007/s00109-012-0883-2.
  63. 63.
    Kuwahara K, Saito Y, Harada M, et al. Involvement of cardiotrophin-1 in cardiac myocyte-nonmyocyte interactions during hypertrophy of rat cardiac myocytes in vitro. Circulation. 1999;100:1116–24.PubMedCrossRefGoogle Scholar
  64. 64.
    Harada M, Itoh H, Nakagawa O, et al. Significance of ventricular myocytes and nonmyocytes interaction during cardiocyte hypertrophy: evidence for endothelin-1 as a paracrine hypertrophic factor from cardiac nonmyocytes. Circulation. 1997;96:3737–44.PubMedCrossRefGoogle Scholar
  65. 65.
    Sano M, Fukuda K, Kodama H, et al. Interleukin-6 family of cytokines mediate angiotensin II-induced cardiac hypertrophy in rodent cardiomyocytes. J Biol Chem. 2000;275:29717–23.PubMedCrossRefGoogle Scholar
  66. 66.
    Shiojima I, Sato K, Izumiya Y, et al. Disruption of coordinated cardiac hypertrophy and angiogenesis contributes to the transition to heart failure. J Clin Invest. 2005;115:2108–18.PubMedCrossRefGoogle Scholar
  67. 67.
    Kazakov A, Muller P, Jagoda P, et al. Endothelial nitric oxide synthase of the bone marrow regulates myocardial hypertrophy, fibrosis, and angiogenesis. Cardiovasc Res. 2012;93:397–405.PubMedCrossRefGoogle Scholar
  68. 68.
    Ventura-Clapier R, Garnier A, Veksler V. Energy metabolism in heart failure. J Physiol. 2004;555:1–13.PubMedCrossRefGoogle Scholar
  69. 69.
    Stanley WC, Recchia FA, Lopaschuk GD. Myocardial substrate metabolism in the normal and failing heart. Physiol Rev. 2005;85:1093–129.PubMedCrossRefGoogle Scholar
  70. 70.
    Turer AT, Malloy CR, Newgard CB, et al. Energetics and metabolism in the failing heart: important but poorly understood. Curr Opin Clin Nutr Metab Care. 2010;13:458–65.PubMedCrossRefGoogle Scholar
  71. 71.
    Ashrafian H, Frenneaux MP, Opie LH. Metabolic mechanisms in heart failure. Circulation. 2007;116:434–48.PubMedCrossRefGoogle Scholar
  72. 72.
    Beer M, Seyfarth T, Sandstede J, et al. Absolute concentrations of high-energy phosphate metabolites in normal, hypertrophied, and failing human myocardium measured noninvasively with (31)P-SLOOP magnetic resonance spectroscopy. J Am Coll Cardiol. 2002;40:1267–74.PubMedCrossRefGoogle Scholar
  73. 73.
    Starling RC, Hammer DF, Altschuld RA. Human myocardial ATP content and in vivo contractile function. Mol Cell Biochem. 1998;180:171–7.PubMedCrossRefGoogle Scholar
  74. 74.
    Taegtmeyer H. Switching metabolic genes to build a better heart. Circulation. 2002;106:2043–5.PubMedCrossRefGoogle Scholar
  75. 75.
    Hue L, Taegtmeyer H. The Randle cycle revisited: a new head for an old hat. Am J Physiol Endocrinol Metab. 2009;297:E578–91.PubMedCrossRefGoogle Scholar
  76. 76.
    Lopaschuk GD, Ussher JR, Folmes CD, et al. Myocardial fatty acid metabolism in health and disease. Physiol Rev. 2010;90:207–58.PubMedCrossRefGoogle Scholar
  77. 77.
    Rosca MG, Hoppel CL. Mitochondria in heart failure. Cardiovasc Res. 2010;88:40–50.PubMedCrossRefGoogle Scholar
  78. 78.
    Ventura-Clapier R, Garnier A, Veksler V. Transcriptional control of mitochondrial biogenesis: the central role of PGC-1alpha. Cardiovasc Res. 2008;79:208–17.PubMedCrossRefGoogle Scholar
  79. 79.
    Arany Z, He H, Lin J, et al. Transcriptional coactivator PGC-1 alpha controls the energy state and contractile function of cardiac muscle. Cell Metab. 2005;1:259–71.PubMedCrossRefGoogle Scholar
  80. 80.
    Arany Z, Novikov M, Chin S, et al. Transverse aortic constriction leads to accelerated heart failure in mice lacking PPAR-gamma coactivator 1alpha. Proc Natl Acad Sci U S A. 2006;103:10086–91.PubMedCrossRefGoogle Scholar
  81. 81.
    Leone TC, Lehman JJ, Finck BN, et al. PGC-1alpha deficiency causes multi-system energy metabolic derangements: muscle dysfunction, abnormal weight control and hepatic steatosis. PLoS Biol. 2005;3:e101.PubMedCrossRefGoogle Scholar
  82. 82.
    Tian R, Musi N, D’Agostino J, et al. Increased adenosine monophosphate-activated protein kinase activity in rat hearts with pressure-overload hypertrophy. Circulation. 2001;104:1664–9.PubMedCrossRefGoogle Scholar
  83. 83.
    Jessen N, Koh HJ, Folmes CD, et al. Ablation of LKB1 in the heart leads to energy deprivation and impaired cardiac function. Biochim Biophys Acta. 2010;1802:593–600.PubMedCrossRefGoogle Scholar
  84. 84.
    Thomson DM, Hancock CR, Evanson BG, et al. Skeletal muscle dysfunction in muscle-specific LKB1 knockout mice. J Appl Physiol. 2010;108:1775–85.PubMedCrossRefGoogle Scholar
  85. 85.
    Ahluwalia A. Tarnawski AS: Activation of the metabolic sensor-AMP activated protein kinase reverses impairment of angiogenesis in aging myocardial microvascular endothelial cells. Implications for the aging heart. J Physiol Pharmacol. 2011;62:583–7.PubMedGoogle Scholar
  86. 86.
    Nagata D, Mogi M, Walsh K. AMP-activated protein kinase (AMPK) signaling in endothelial cells is essential for angiogenesis in response to hypoxic stress. J Biol Chem. 2003;278:31000–6.PubMedCrossRefGoogle Scholar
  87. 87.
    Ohashi K, Ouchi N, Higuchi A, et al. LKB1 deficiency in Tie2-Cre-expressing cells impairs ischemia-induced angiogenesis. J Biol Chem. 2010;285:22291–8.PubMedCrossRefGoogle Scholar
  88. 88.
    Li J, Hu X, Selvakumar P, et al. Role of the nitric oxide pathway in AMPK-mediated glucose uptake and GLUT4 translocation in heart muscle. Am J Physiol Endocrinol Metab. 2004;287:E834–41.PubMedCrossRefGoogle Scholar
  89. 89.
    Gschwend S, Henning RH, Pinto YM, et al. Myogenic constriction is increased in mesenteric resistance arteries from rats with chronic heart failure: instantaneous counteraction by acute AT1 receptor blockade. Br J Pharmacol. 2003;139:1317–25.PubMedCrossRefGoogle Scholar
  90. 90.
    Horman S, Morel N, Vertommen D, et al. AMP-activated protein kinase phosphorylates and desensitizes smooth muscle myosin light chain kinase. J Biol Chem. 2008;283:18505–12.PubMedCrossRefGoogle Scholar
  91. 91.
    Zannad F, Alla F, Dousset B, et al. Limitation of excessive extracellular matrix turnover may contribute to survival benefit of spironolactone therapy in patients with congestive heart failure: insights from the randomized aldactone evaluation study (RALES). Rales Investigators. Circulation. 2000;102:2700–6.PubMedCrossRefGoogle Scholar
  92. 92.
    Webb CS, Bonnema DD, Ahmed SH, et al. Specific temporal profile of matrix metalloproteinase release occurs in patients after myocardial infarction: relation to left ventricular remodeling. Circulation. 2006;114:1020–7.PubMedCrossRefGoogle Scholar
  93. 93.
    Morizane Y, Thanos A, Takeuchi K, et al. AMP-activated protein kinase suppresses matrix metalloproteinase-9 expression in mouse embryonic fibroblasts. J Biol Chem. 2011;286:16030–8.PubMedCrossRefGoogle Scholar
  94. 94.
    Mishra R, Cool BL, Laderoute KR, et al. AMP-activated protein kinase inhibits transforming growth factor-beta-induced Smad3-dependent transcription and myofibroblast transdifferentiation. J Biol Chem. 2008;283:10461–9.PubMedCrossRefGoogle Scholar
  95. 95.
    Zheng B, Cantley LC. Regulation of epithelial tight junction assembly and disassembly by AMP-activated protein kinase. Proc Natl Acad Sci U S A. 2007;104:819–22.PubMedCrossRefGoogle Scholar
  96. 96.
    Zhang L, Li J, Young LH, et al. AMP-activated protein kinase regulates the assembly of epithelial tight junctions. Proc Natl Acad Sci U S A. 2006;103:17272–7.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Sandrine Horman
    • 1
  • Christophe Beauloye
    • 1
  • Jean-Louis Vanoverschelde
    • 1
  • Luc Bertrand
    • 1
    Email author
  1. 1.Institut de Recherche Expérimentale et Clinique, Pôle de Recherche CardiovasculaireUniversité Catholique de Louvain, IREC/CARDBrusselsBelgium

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