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Heart Sphingolipids in Health and Disease

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Sphingolipids and Metabolic Disease

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 721))

Abstract

In recent years, the role of sphingolipids in physiology and pathophysiology of the heart attracted much attention. Ceramide was found to be involved in the pathogenesis of cardiac dysfunction in animal models of ischemia/reperfusion injury, Type 2 diabetes and lipotoxic cardiomyopathy. On the other hand, another member of this lipid family, namely sphingosine-1-phosphate, has been shown to possess potent cardioprotective properties. This chapter provides a review of the role of ceramide and other bioactive sphingolipids in physiology and pathophysiology of the heart. We describe the role of PPARs and exercise in regulation of myocardial sphingolipid metabolism. We also summarize the present state of knowledge on the involvement of ceramide and sphingosine-1-phosphate in the development and prevention of ischemia/reperfusion injury of the heart. In the last section of this chapter we discuss the evidence for a role of ceramide in myocardial lipotoxicity.

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References

  1. Okazaki T, Bielawska A, Bell RM et al. Role of ceramide as a lipid mediator of 1 alpha,25-dihydroxyvitamin D3-induced HL-60 cell differentiation. J Biol Chem 1990; 265:15823–15831.

    PubMed  CAS  Google Scholar 

  2. Yang J, Yu Y, Sun S et al. Ceramide and other sphingolipids in cellular responses. Cell Biochem Biophys 2004; 40:323–350.

    Article  PubMed  CAS  Google Scholar 

  3. Summers SA. Ceramides in insulin resistance and lipotoxicity. Prog Lipid Res 2005; 45:42–72.

    Article  PubMed  Google Scholar 

  4. Baranowski M, Zabielski P, Blachnio A et al. Effect of exercise duration on ceramide metabolism in the rat heart. Acta Physiol (Oxf) 2008; 192:519–529.

    Article  CAS  Google Scholar 

  5. Baranowski M, Blachnio-Zabielska A, Hirnle T et al. Myocardium of type 2 diabetic and obese patients is characterized by alterations in sphingolipid metabolic enzymes but not by accumulation of ceramide. J Lipid Res 2010; 51:74–80.

    Article  PubMed  Google Scholar 

  6. Li CM, Hong SB, Kopal G et al. Cloning and characterization of the full-length cDNA and genomic sequences encoding murine acid ceramidase. Genomics 1998; 50:267–274.

    Article  PubMed  CAS  Google Scholar 

  7. Li CM, Park JH, He X et al. The human acid ceramidase gene (ASAH): structure, chromosomal location, mutation analysis and expression. Genomics 1999; 62:223–231.

    Article  PubMed  CAS  Google Scholar 

  8. Liu H, Sugiura M, Nava VE et al. Molecular cloning and functional characterization of a novel mammalian sphingosine kinase type 2 isoform. J Biol Chem 2000; 275:19513–19520.

    Article  PubMed  CAS  Google Scholar 

  9. Yang Q, Li Y. Roles of PPARs on regulating myocardial energy and lipid homeostasis. J Mol Med 2007; 85:697–706.

    Article  PubMed  CAS  Google Scholar 

  10. Finck BN, Han X, Courtois M et al. A critical role for PPARalpha-mediated lipotoxicity in the pathogenesis of diabetic cardiomyopathy: modulation by dietary fat content. ProcNatl Acad Sci USA 2003; 100:1226–1231.

    Article  CAS  Google Scholar 

  11. Baranowski M, Blachnio A, Zabielski P et al. PPARalpha agonist induces the accumulation of ceramide in the heart of rats fed high-fat diet. J Physiol Pharmacol 2007; 58:57–72.

    PubMed  CAS  Google Scholar 

  12. Rivier M, Castiel I, Safonova I et al. Peroxisome proliferator-activated receptor-alpha enhances lipid metabolism in a skin equivalent model. J Invest Dermatol 2000; 114:681–687.

    Article  PubMed  CAS  Google Scholar 

  13. Bahr M, Spelleken M, Bock M et al. Acute and chronic effects of troglitazone (CS-045) on isolated rat ventricular cardiomyocytes. Diabetologia 1996; 39:766–774.

    Article  PubMed  CAS  Google Scholar 

  14. Sidell RJ, Cole MA, Draper NJ et al. Thiazolidinedione treatmentnormalizes insulin resistance and ischemic injury in the zucker Fatty rat heart. Diabetes 2002; 51:1110–1117.

    Article  PubMed  CAS  Google Scholar 

  15. Oakes ND, Kennedy CJ, Jenkins AB et al. A new antidiabetic agent, BRL 49653, reduces lipid availability and improves insulin action and glucoregulation in the rat. Diabetes 1994; 43:1203–1210.

    Article  PubMed  CAS  Google Scholar 

  16. Carley AN, Semeniuk LM, Shimoni Y et al. Treatment of type 2 diabetic db/db mice with a novel PPARgamma agonist improves cardiac metabolism but not contractile function. Am J Physiol Endocrinol Metab 2004; 286:E449–E455.

    Article  PubMed  CAS  Google Scholar 

  17. Liu LS, Tanaka H, Ishii S et al. The new antidiabetic drug Mcc-555 acutely sensitizes insulin signaling in isolated cardiomyocytes. Endocrinology 1998; 139:4531–4539.

    Article  PubMed  CAS  Google Scholar 

  18. Zhou YT, Grayburn P, Karim A et al. Lipotoxic heart disease in obese rats: implications for human obesity. Proc Natl Acad Sci USA 2000; 97:1784–1789.

    Article  PubMed  CAS  Google Scholar 

  19. Hanada K. Serine palmitoyltransferase, a key enzyme of sphingolipid metabolism. Biochim Biophys Acta 2003; 1632:16–30.

    PubMed  CAS  Google Scholar 

  20. Shimabukuro M, Higa M, Zhou YT et al. Lipoapoptosis in beta-cells of obese prediabetic fa/fa rats. Role of serine palmitoyltransferase overexpression. J Biol Chem 1998; 273:32487–32490.

    Article  PubMed  CAS  Google Scholar 

  21. Blazquez C, Geelen MJ, Velasco G et al. The AMP-activated protein kinase prevents ceramide synthesis de novo and apoptosis in astrocytes. FEBS Lett 2001; 489:149–153.

    Article  PubMed  CAS  Google Scholar 

  22. Liu L, Shi X, Bharadwaj KG et al. DGAT1 expression increases heart triglyceride content but ameliorates lipotoxicity. J Biol Chem 2009; 284:36312–36323.

    Article  PubMed  CAS  Google Scholar 

  23. Sabbadini RA, Danieli-Betto D, Betto R. The role of sphingolipids in the control of skeletal muscle function: a review. Ital J Neurol Sci 1999; 20:423–430.

    PubMed  CAS  Google Scholar 

  24. Dobrzyn A, Gorski J. Effect of acute exercise on the content of free sphinganine and sphingosine in different skeletal muscle types of the rat. Horm Metab Res 2002; 34:523–529.

    Article  PubMed  CAS  Google Scholar 

  25. McDonough PM, Yasui K, Betto R et al. Control of cardiac Ca2+ levels. Inhibitory actions of sphingosine on ca2+ transients and L-type ca2+ channel conductance. Circ Res 1994; 75:981–989.

    PubMed  CAS  Google Scholar 

  26. Sharma C, Smith T, Li S et al. Inhibition of Ca2+ release channel (ryanodine receptor) activity by sphingolipid bases: mechanism of action. Chem Phys Lipids 2000; 104:1–11.

    Article  PubMed  CAS  Google Scholar 

  27. Dawson E, George K, Shave R et al. Does the human heart fatigue subsequent to prolonged exercise? Sports Med 2003; 33:365–380.

    Article  PubMed  Google Scholar 

  28. Krown KA, Page MT, Nguyen C et al. Tumor necrosis factor alpha-induced apoptosis in cardiac myocytes. Involvement of the sphingolipid signaling cascade in cardiac cell death. J Clin Invest 1996; 98:2854–2865.

    Article  PubMed  CAS  Google Scholar 

  29. Bielawska AE, Shapiro JP, Jiang L et al. Ceramide is involved in triggering of cardiomyocyte apoptosis induced by ischemia and reperfusion. Am J Pathol 1997; 151:1257–1263.

    PubMed  CAS  Google Scholar 

  30. Zhang DX, Fryer RM, Hsu AK et al. Production and metabolism of ceramide in normal and ischemic-reperfused myocardium of rats. Basic Res Cardiol 2001; 96:267–274.

    Article  PubMed  CAS  Google Scholar 

  31. Cordis GA, Yoshida T, Das DK. HPTLC analysis of sphingomylein, ceramide and sphingosine in ischemic/ reperfused rat heart. J Pharm Biomed Anal 1998; 16:1189–1193.

    Article  PubMed  CAS  Google Scholar 

  32. Argaud L, Prigent AF, Chalabreysse L et al. Ceramide in the antiapoptotic effect of ischemic preconditioning. Am J Physiol Heart Circ Physiol 2004; 286:H246–H251.

    Article  PubMed  CAS  Google Scholar 

  33. Beresewicz A, Dobrzyn A, Gorski J. Accumulation of specific ceramides in ischemic/reperfused rat heart; effect of ischemic preconditioning. J Physiol Pharmacol 2002; 53:371–382.

    PubMed  CAS  Google Scholar 

  34. Hernandez OM, Discher DJ, Bishopric NH et al. Rapid activation of neutral sphingomyelinase by hypoxia-reoxygenation of cardiac myocytes. Circ Res 2000; 86:198–204.

    PubMed  CAS  Google Scholar 

  35. Jessup W. Lipid metabolism: sources and stability of plasma sphingosine-1-phosphate. Curr Opin Lipidol 2008; 19:543–534.

    Article  PubMed  CAS  Google Scholar 

  36. Karliner JS. Sphingosine kinase and sphingosine 1-phosphate in cardioprotection. J Cardiovasc Pharmacol 2009; 53:189–197.

    Article  PubMed  CAS  Google Scholar 

  37. Means CK, Brown JH. Sphingosine-1-phosphate receptor signalling in the heart. Cardiovasc Res 2009; 82:193–200.

    Article  PubMed  CAS  Google Scholar 

  38. Karliner JS, Honbo N, Summers K et al. The lysophospholipids sphingosine-1-phosphate and lysophosphatidic acid enhance survival during hypoxia in neonatal rat cardiac myocytes. J Mol cell cardiol 2001;33:1713–1717.

    Article  PubMed  CAS  Google Scholar 

  39. Lecour S, Smith RM, Woodward B et al. Identification of a novel role for sphingolipid signaling in TNF alpha and ischemic preconditioning mediated cardioprotection. J Mol Cell Cardiol 2002; 34:509–518.

    Article  PubMed  CAS  Google Scholar 

  40. Jin ZQ, Zhou HZ, Zhu P et al. Cardioprotection mediated by sphingosine-1-phosphate and ganglioside GM-1 in wild-type and PKC epsilon knockout mouse hearts. Am J Physiol Heart Circ Physiol 2002; 282:H1970–H1977.

    PubMed  CAS  Google Scholar 

  41. Tao R, Zhang J, Vessey DA et al. Deletion of the sphingosine kinase-1 gene influences cell fate during hypoxia and glucose deprivation in adult mouse cardiomyocytes. Cardiovasc Res 2007; 74:56–63.

    Article  PubMed  CAS  Google Scholar 

  42. Vessey DA, Kelley M, Li L et al. Role of sphingosine kinase activity in protection of heart against ischemia reperfusion injury. Med Sci Monit 2006; 12:BR318–BR324.

    PubMed  CAS  Google Scholar 

  43. Jin ZQ, Zhang J, Huang Y et al. A sphingosine kinase 1 mutation sensitizes the myocardium to ischemia/ reperfusion injury. Cardiovasc Res 2007; 76:41–50.

    Article  PubMed  CAS  Google Scholar 

  44. Duan HF, Wang H, Yi J et al. Adenoviral gene transfer of sphingosine kinase 1 protects heart against ischemia/ reperfusion-induced injury and attenuates its postischemic failure. Hum Gene Ther 2007; 18:1119–1128.

    Article  PubMed  CAS  Google Scholar 

  45. Kennedy S, Kane KA, Pyne NJ et al. Targeting sphingosine-1-phosphate signalling for cardioprotection. Curr Opin Pharmacol 2009; 9:194–201.

    Article  PubMed  CAS  Google Scholar 

  46. Vessey DA, Li L, Kelley M et al. Sphingosine can pre and postcondition heart and utilizes a different mechanism from sphingosine 1-phosphate. J Biochem Mol Toxicol 2008; 22:113–118.

    Article  PubMed  CAS  Google Scholar 

  47. Zhang J, Honbo N, Goetzl EJ et al. Signals from type 1 sphingosine 1-phosphate receptors enhance adult mouse cardiac myocyte survival during hypoxia. Am J Physiol Heart Circ Physiol 2007; 293:H3150–H3158.

    Article  PubMed  CAS  Google Scholar 

  48. Means CK, Xiao CY, Li Z et al. Sphingosine 1-phosphate S1P2 and S1P3 receptor-mediated Akt activation protects against in vivo myocardial ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol 2007; 292:H2944–H2951.

    Article  PubMed  CAS  Google Scholar 

  49. Theilmeier G, Schmidt C, Herrmann J et al. High-density lipoproteins and their constituent, sphingosine-1-phosphate, directly protect the heart against ischemia/reperfusion injury in vivo via the S1P3 lysophospholipid receptor. Circulation 2006; 114:1403–1409.

    Article  PubMed  CAS  Google Scholar 

  50. Hofmann U, Burkard N, Vogt C et al. Protective effects of sphingosine-1-phosphate receptor agonist treatment after myocardial ischaemia-reperfusion. Cardiovasc Res 2009; 83:285–293.

    Article  PubMed  CAS  Google Scholar 

  51. Tsukada YT, Sanna MG, Rosen H et al. S1P1-selective agonist SEW2871 exacerbates reperfusionarrhythmias. J cardiovasc Pharmacol 2007; 50:660–669.

    Article  PubMed  CAS  Google Scholar 

  52. Jin ZQ, Goetzl EJ, Karliner JS. Sphingosine kinase activation mediates ischemic preconditioning in murine heart. Circulation 2004; 110:1980–1989.

    Article  PubMed  CAS  Google Scholar 

  53. Vessey DA, Li L, Honbo N et al. Sphingosine 1-phosphate is an important endogenous cardioprotectant released by ischemic pre and postconditioning. Am J Physiol Heart Circ Physiol 2009; 297:H1429–H1435.

    Article  PubMed  CAS  Google Scholar 

  54. Jin ZQ, Karliner JS, Vessey DA. Ischaemic postconditioning protects isolated mouse hearts against ischaemia/ reperfusion injury via sphingosine kinase isoform-1 activation. Cardiovasc Res 2008; 79:134–140.

    Article  PubMed  CAS  Google Scholar 

  55. Knapp M, Baranowski M, Czarnowski D et al. Plasma sphingosine-1-phosphate concentration is reduced in patients with myocardial infarction. Med Sci Monit 2009; 15:CR490–CR493.

    PubMed  CAS  Google Scholar 

  56. Borradaile NM, Schaffer JE. Lipotoxicity in the heart. Curr Hypertens Rep 2005; 7:412–417.

    Article  PubMed  CAS  Google Scholar 

  57. Harmancey R, Wilson CR, Taegtmeyer H. Adaptation and maladaptation of the heart in obesity. Hypertension 2008; 52:181–187.

    Article  PubMed  CAS  Google Scholar 

  58. Young ME, McNulty P, Taegtmeyer H. Adaptation and maladaptation of the heart in diabetes: Part II: potential mechanisms. Circulation 2002; 105:1861–1870.

    Article  PubMed  CAS  Google Scholar 

  59. Park TS, Yamashita H, Blaner WS et al. Lipids in the heart: a source of fuel and a source of toxins. Curr Opin Lipidol 2007; 18:277–282.

    Article  PubMed  CAS  Google Scholar 

  60. Chiu HC, Kovacs A, Ford DA et al. A novel mouse model of lipotoxic cardiomyopathy. J Clin Invest 2001; 107:813–822.

    Article  PubMed  CAS  Google Scholar 

  61. Chiu HC, Kovacs A, Blanton RM et al. Transgenic expression of fatty acid transport protein 1 in the heart causes lipotoxic cardiomyopathy. Circ Res 2005; 96:225–233.

    Article  PubMed  CAS  Google Scholar 

  62. Yagyu H, Chen G, Yokoyama M et al. Lipoprotein lipase (LpL) on the surface of cardiomyocytes increases lipid uptake and produces a cardiomyopathy. J Clin Invest 2003; 111:419–426.

    PubMed  Google Scholar 

  63. Son NH, Park TS, Yamashita H et al. Cardiomyocyte expression of PPARgamma leads to cardiac dysfunction in mice. J Clin Invest 2007; 117:2791–2801.

    Article  PubMed  CAS  Google Scholar 

  64. Park TS, Hu Y, Noh HL et al. Ceramide is a cardiotoxin in lipotoxic cardiomyopathy. J Lipid Res 2008; 49:2101–2112.

    Article  PubMed  CAS  Google Scholar 

  65. Basu R, Oudit GY, Wang X et al. Type 1 diabetic cardiomyopathy in the Akita (Ins2WT/C96Y) mouse model is characterized by diastolic dysfunction with preserved systolic function. Am J Physiol Heart Circ Physiol 2009; 297:H2096–H2108.

    Article  PubMed  CAS  Google Scholar 

  66. Foo RS, Mani K, Kitsis RN. Death begets failure in the heart. J Clin Invest 2005; 115:565–571.

    PubMed  CAS  Google Scholar 

  67. Boudina S, Abel ED. Diabetic cardiomyopathy revisited. Circulation 2007; 115:3213–3223.

    Article  PubMed  Google Scholar 

  68. Dyntar D, Eppenberger-Eberhardt M, Maedler K et al. Glucose and palmitic acid induce degeneration of myofibrils and modulate apoptosis in rat adult cardiomyocytes. Diabetes 2001; 50:2105–2113.

    Article  PubMed  CAS  Google Scholar 

  69. Hickson-Bick DL, Buja ML, McMillin JB. Palmitate-mediated alterations in the fatty acid metabolism of rat neonatal cardiac myocytes. J Mol cell Cardiol 2000; 32:511–519.

    Article  PubMed  CAS  Google Scholar 

  70. Torre-Villalvazo I, Gonzalez F, Aguilar-Salinas CA et al. Dietary soy protein reduces cardiac lipid accumulation and the ceramide concentration in high-fat diet-fed rats and ob/ob mice. J Nutr 2009; 139:2237–2243.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Physiology, Medical University of Białystok, Białystok, Poland

    Marcin Baranowski & Jan Górski

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  1. Marcin Baranowski
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  2. Jan Górski
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  1. Department of Biochemistry and Molecular Biology, Medical University of South Carolina, and Ralph H. Johnson Veteran’s Administration, Charleston, South Carolina, USA

    L. Ashley Cowart PhD

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Baranowski, M., Górski, J. (2011). Heart Sphingolipids in Health and Disease. In: Cowart, L.A. (eds) Sphingolipids and Metabolic Disease. Advances in Experimental Medicine and Biology, vol 721. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-0650-1_3

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