**Author details**

Luca Siracusano\* and Viviana Girasole

*Department of Neuroscience, Psychiatric and Anesthesiological Sciences, University of Messina, School of Medicine, Policlinico Universitario G. Martino, Italy* 

The Role of Altered Lipid Metabolism in Septic Myocardial Dysfunction 349

[15] Zhao P, Wang J, He L, Ma H, Zhang X, Zhu X, et al: Deficiency in TLR4 signal transduction ameliorates cardiac injury and cardiomyocyte contractile dysfunction

[16] Calfee CS, Matthay MA: Clinical immunology: Culprits with evolutionary ties. Nature.

[17] Könner AC, Brüning JC: Toll-like receptors: linking inflammation to metabolism.

[18] Langouche L, Perre SV, Thiessen S, Gunst J, Hermans G, D'Hoore A, Kola B, Korbonits M, Van den Berghe G: Alterations in adipose tissue during critical illness: An adaptive

[19] Siracusano L, Girasole V: Sepsis and Adiponectin. In: Masayoshi Y (Ed): Adiponectin:

[20] van der Poll T: Experimental human sepsis models. Drug Discovery Today: Disease

[21] Weissman C: The metabolic response to stress: an overview and update.

[22] Biolo G, Toigo G, Ciocchi B, Situlin R, Iscra F, Gullo A, Guarnieri G: Metabolic response to injury and sepsis: changes in protein metabolism. Nutrition. 1997 Sep;13(9

[23] Tappy L, Chioléro R: Substrate utilization in sepsis and multiple organ failure. Crit Care

[24] Li L, Messina JL: Acute insulin resistance following injury. Trends Endocrinol Metab.

[25] Mittra S, Bansal VS, Bhatnagar PK: From a glucocentric to a lipocentric approach

[26] Unger RH, Clark GO, Scherer PE, Orci L: Lipid homeostasis, lipotoxicity and the

[27] Duska F, Andel M: Intensive blood glucose control in acute and prolonged critical illness: endogenous secretion contributes more to plasma insulin than exogenous

[28] Van den Berghe G: How does blood glucose control with insulin save lives in intensive

[29] Crouser ED: Mitochondrial dysfunction in septic shock and multiple organ dysfunction

[30] Karpac J, Jasper H: Insulin and JNK: optimizing metabolic homeostasis and lifespan.

[31] Drosatos K, Drosatos-Tampakaki Z, Khan R, Homma S, Schulze PC, Zannis VI, Goldberg IJ: Inhibition of c-Jun-N-terminal kinase increases cardiac peroxisome proliferatoractivated receptor alpha expression and fatty acid oxidation and prevents lipopolysaccharide-induced heart dysfunction. J Biol Chem. 2011 Oct 21;286(42):36331-9. [32] van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R: Intensive insulin therapy in

towards metabolic syndrome. Drug Discov Today. 2008 Mar;13(5-6):211-8.

metabolic syndrome. Biochim Biophys Acta. 2010 Mar;1801(3):209-14.

insulin infusion. Metabolism. 2008 May;57(5):669-71.

care? J Clin Invest 2004; 114:1187–1195.

syndrome. Mitochondrion. 2004 ; 4:729-41.

Trends Endocrinol Metab. 2009 Apr;20(3):100-6.

critically ill patients. N Engl J Med. 2001 Nov 8;345(19):1359-67.

during ischemia. J Cell Mol Med 2009;13:1513–25.

Trends Endocrinol Metab. 2011 Jan;22(1):16-23.

Anesthesiology. 1990 Aug;73(2):308-27.

Med 2007; 35[Suppl.]:S531–S534.

and protective response? Am J Respir Crit Care Med. 2010 Aug.

Production, Regulation and Roles in Disease. Nova Publishers At Press.

2010 Mar 4;464(7285):41-2.

Models, 2012:9;e3-e9.

Suppl):52S-57S.

2009 Nov;20(9):429-35.

## **10. References**


<sup>\*</sup> Corresponding Author

[15] Zhao P, Wang J, He L, Ma H, Zhang X, Zhu X, et al: Deficiency in TLR4 signal transduction ameliorates cardiac injury and cardiomyocyte contractile dysfunction during ischemia. J Cell Mol Med 2009;13:1513–25.

348 Lipid Metabolism

**Author details** 

and Viviana Girasole

*School of Medicine, Policlinico Universitario G. Martino, Italy* 

associated costs of care. Crit Care Med. 2001;29:1303–1310.

*Department of Neuroscience, Psychiatric and Anesthesiological Sciences, University of Messina,* 

[1] Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome and

[2] Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G; SCCM/ESICM/ACCP/ATS/SIS: 2001 SCCM/ESICM/ACCP /ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003

[3] Cinel I, Opal SM: Molecular biology of inflammation and sepsis: a primer. Crit Care

[4] Boomer JS, To K, Chang KC, Takasu O, Osborne DF, Walton AH, Bricker TL, Jarman SD 2nd, Kreisel D, Krupnick AS, Srivastava A, Swanson PE, Green JM, Hotchkiss RS: Immunosuppression in patients who die of sepsis and multiple organ failure. JAMA.

[5] Skrupky LP, Kerby PW, Hotchkiss RS: Advances in the management of sepsis and the understanding of key immunologic defects. Anesthesiology. 2011 Dec;115(6):1349-62 [6] Shubin NJ, Monaghan SF, Ayala A: Anti-inflammatory mechanisms of sepsis. Contrib

[7] Lorne E, Dupont H, Abraham E: Toll-like receptors 2 and 4: initiators of non-septic inflammation in critical care medicine? Intensive Care Med. 2010 Nov;36(11):1826-35. [8] Skrupky LP, Kerby PW, Hotchkiss RS: Advances in the management of sepsis and the understanding of key immunologic defects. Anesthesiology. 2011 Dec;115(6):1349-62. [9] van der Poll T, van Zoelen MA, Wiersinga WJ: Regulation of pro-and anti-inflammatory

[10] Biswas SK, Lopez-Collazo E: Endotoxin tolerance: new mechanisms, molecules and

[11] McCall CE, Yoza B, Liu T, El Gazzar M: Gene-specific epigenetic regulation in serious

[12] Alves-Filho JC, Spiller F, Cunha FQ: Neutrophil paralysis in sepsis. Shock. 2010 Sep;34

[13] Vartanian K, Stenzel-Poore M: Toll-like receptor tolerance as a mechanism for

[14] Frantz S, Ertl G, Bauersachs J: Mechanisms of disease: Toll-like receptors in cardiovascular disease. Nat Clin Pract Cardiovasc Med. 2007 Aug;4(8):444-54.

infections with systemic inflammation. J Innate Immun. 2010;2(5):395-405

Luca Siracusano\*

**10. References** 

Apr;31(4):1250-6.

Med. 2009 Jan;37(1):291-304.

2011 Dec 21;306(23):2594-605.

Microbiol. 2011;17:108-24.

Suppl 1:15-21.

Corresponding Author

 \* host responses. Contrib Microbiol. 2011;17:125-36.

clinical significance. Trends Immunol. 2009 Oct;30(10):475-87.

neuroprotection. Transl Stroke Res. 2010 Dec 1;1(4):252-260.


[33] NICE-SUGAR Study Investigators, Finfer S, Chittock DR, Su SY, Blair D, Foster D, Dhingra V, Bellomo R, Cook D, Dodek P, Henderson WR, Hébert PC, Heritier S, Heyland DK, McArthur C, McDonald E, Mitchell I, Myburgh JA, Norton R, Potter J, Robinson BG, Ronco JJ: Intensive versus conventional glucose control in critically ill patients.

The Role of Altered Lipid Metabolism in Septic Myocardial Dysfunction 351

[52] Sheperd PR, Kahn BB: Glucose transporters and insulin action. Implications for Insulin

[53] Friehs I, Moran AM, Stamm C, Colan SD, Takeuchi K, Cao-Danh H, Rader CM, McGowan FX, del Nido PJ: Impaired glucose transporter activity in pressure-overload

[55] Taegtmeyer H, Sen S, Vela D: Return to the fetal gene program: a suggested metabolic

[56] van Uden P, Kenneth NS, Rocha S: Regulation of hypoxia-inducible factor-1alpha by

[57] Kuhlicke J, Frick JS, Morote-Garcia JC, Rosenberger P, Eltzschig HK: Hypoxia inducible factor (HIF)-1 coordinates induction of Toll-like receptors TLR2 and TLR6 during

[58] Semenza GL. Regulation of oxygen homeostasis by hypoxia-inducible factor 1.

[59] Narravula S, Colgan SP: Hypoxia-inducible factor 1-mediated inhibition of peroxisome proliferator-activated receptor alpha expression during hypoxia. J Immunol. 2001 Jun

[60] Krishnan J, Suter M, Windak R, Krebs T, Felley A, Montessuit C, Tokarska-Schlattner M, Aasum E, Bogdanova A, Perriard E, Perriard JC, Larsen T, Pedrazzini T, Krek W: Activation of a HIF1alpha-PPARgamma axis underlies the integration of glycolytic and lipid anabolic pathways in pathologic cardiac hypertrophy. Cell Metab. 2009

[61] Cadenas S, Aragonés J, Landázuri MO: Mitochondrial reprogramming through cardiac oxygen sensors in ischaemic heart disease. Cardiovasc Res. 2010 Nov 1;88(2):219-28. [62] Kominsky DJ, Campbell EL, Colgan SP: Metabolic shifts in immunity and

[63] Haigis MC, Sinclair DA: Mammalian sirtuins: biological insights and disease relevance.

[64] Rahman S, Islam R: Mammalian Sirt1: insights on its biological functions. Cell Commun

[65] Cantó C, Auwerx J: Targeting sirtuin 1 to improve metabolism: all you need is NAD(+)?

[66] Cantó C, Auwerx J: PGC-1alpha, SIRT1 and AMPK, an energy sensing network that

[67] Borradaile NM, Pickering JG: NAD(+), sirtuins, and cardiovascular disease. Curr Pharm

[68] Menzies KJ, Hood DA: The role of SirT1 in muscle mitochondrial turnover.

[69] Rane S, He M, Sayed D, Vashistha H, Malhotra A, Sadoshima J, Vatner DE, Vatner SF, Abdellatif M: Downregulation of miR-199a derepresses hypoxia-inducible factor-1alpha and Sirtuin 1 and recapitulates hypoxia preconditioning in cardiac myocytes. Circ Res.

controls energy expenditure. Curr Opin Lipidol. 2009 Apr;20(2):98-105.

link to gene expression in the heart. Ann N Y Acad Sci. 2010 Feb; 1188:191-8.

Resistance and Diabetes Mellitus. N Engl J Med 2003; 341:248–257.

hypertrophy is an early indicator of progression to failure.

NF-kappaB. Biochem J. 2008 Jun 15;412(3):477-84.

inflammation. J Immunol. 2010 Apr 15;184(8):4062-8.

Annu Rev Pathol. 2010;5:253-95.

Pharmacol Rev. 2012 Jan;64(1):166-87.

Mitochondrion. 2012 Jan;12(1):5-13.

Signal. 2011 May 8;9:11.

Des. 2009;15(1):110-7.

2009 Apr 10;104(7):879-86.

hypoxia. PLoS One. 2007 Dec 26;2(12):e1364.

Physiology (Bethesda) 2009;24:97–106.

15;166(12):7543-8.

Jun;9(6):512-24.

[54] Circulation 1999; 100:II187–II193.


350 Lipid Metabolism

patients.

21.

[34] N Engl J Med. 2009 Mar 26;360(13):1283-97.

Physiol. 2008 15;586:1767-75.

Biol. Lipids2005: 1736;163–180.

1:785–789.

Acta Anaesthesiol Scand. 2009 Mar;53(3):413-14.

biology. Curr Opin Lipidol. 2012 Feb;23(1):35-42.

Physiol Endocrinol Metab. 2009;297:E578–E591.

the heart. Ann NY Acad Sci 2005; 1047:208-18.

translocation. Trends Biochem Sci. 2006 Apr;31(4):215-22.

diabetic cardiomyopathy. Cardiovasc Res. 2011 Oct 1;92(1):10-8.

Normal and Failing Heart. Physiol Rev 2005; 85:1093–1129.

[33] NICE-SUGAR Study Investigators, Finfer S, Chittock DR, Su SY, Blair D, Foster D, Dhingra V, Bellomo R, Cook D, Dodek P, Henderson WR, Hébert PC, Heritier S, Heyland DK, McArthur C, McDonald E, Mitchell I, Myburgh JA, Norton R, Potter J, Robinson BG, Ronco JJ: Intensive versus conventional glucose control in critically ill

[35] Egi M, Finfer S, Bellomo R: Glycemic control in the ICU. Chest. 2011 Jul;140(1):212-20. [36] Dyson A, Stidwill R, Taylor V, Singer M: Tissue oxygen monitoring in rodent models of

[37] Levy B: Lactate and shock state: the metabolic view. Curr Opin Crit Care. 2006 ;12:315-

[38] Holness MJ, Sugden MC: Regulation of pyruvate dehydrogenase complex activity by

[39] Alamdari N, Constantin-Teodosiu D, Murton AJ, Gardiner SM, Bennett T, Layfield R, Greenhaff PL: Temporal changes in the involvement of pyruvate dehydrogenase complex in muscle lactate accumulation during lipopolysaccharide infusion in rats. J

[40] Siracusano L, Girasole V: Glucose and lipid metabolism in sepsis and endotoxemia.

[41] Stanley WC, Recchia F, Lopaschuk GD: Myocardial Substrate Metabolism in the

[42] Davies BS, Beigneux AP, Fong LG, Young SG: New wrinkles in lipoprotein lipase

[43] Koonen, D.P., Glatz, J.F., Bonen, A., Luiken, J: Long-chain fatty acid uptake and FAT/CD36 translocation in heart and skeletal muscle. Biochim. Biophys. Acta, Mol. Cell

[44] Lopaschuk GD, Ussher JR, Folmes CD, Jaswal JS, Stanley WC: Myocardial fatty acid

[45] Randle PJ, Garland PB, Hales CN, Newsholme EA. The glucose-fatty acid cycle: its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1963;

[46] Hue L, Taegtmeyer H. The Randle cycle revisited: a new head for an old hat. Am J

[47] Shuldiner AR, McLenithan JC: Genes and pathophysiology of type 2 diabetes: more

[48] Watson RT, Pessin JE: Bridging the GAP between insulin signaling and GLUT4

[49] Rajabi M, Kassiotis EC, Razeghi P, Taegtmeyer H: Return to the fetal gene program protects the stressed heart: a strong hypothesis. Heart Fail Rev 2007; 12:331–343. [50] van de Weijer T, Schrauwen-Hinderling VB, Schrauwen P: Lipotoxicity in type 2

[51] Taegtmeyer H, Wilson CR, Razeghi P, Sharma S: Metabolic energetics and genetics in

than just the Randle cycle all over again. J Clin Invest 2004;114: 1414–1417.

metabolism in health and disease. Physiol Rev. 2010 Jan;90(1):207-58.

shock. Am J Physiol Heart Circ Physiol. 2007 Jul;293(1):H526-33.

reversible phosphorylation. Biochem Soc Trans. 2003 ;31 :1143-51.


[70] Lee J, Kemper JK: Controlling SIRT1 expression by microRNAs in health and metabolic disease. Aging (Albany NY). 2010 Aug;2(8):527-34.

The Role of Altered Lipid Metabolism in Septic Myocardial Dysfunction 353

[88] Lampidonis AD, Rogdakis E, Voutsinas GE, Stravopodis DJ: The resurgence of Hormone-Sensitive Lipase (HSL) in mammalian lipolysis. Gene. 2011 May 15;477(1-2):1-

[89] Shen WJ, Yu Z, Patel S, Jue D, Liu LF, Kraemer FB: Hormone-sensitive lipase modulates adipose metabolism through PPARγ. Biochim Biophys Acta. 2011 Jan;1811(1):9-16. [90] Chen X, Xun K, Chen L, Wang Y. TNF-alpha, a potent lipid metabolism regulator. Cell

[91] Cawthorn WP, Sethi JK: TNF-alpha and adipocyte biology. FEBS Lett. 2008 Jan

[92] Zhang T, He J, Xu C, Zu L, Jiang H, Pu S, Guo X, Xu G: Mechanisms of metformin inhibiting lipolytic response to isoproterenol in primary rat adipocytes. J Mol

[93] Zu L, He J, Jiang H, Xu C, Pu S, Xu G: Bacterial endotoxin stimulates adipose lipolysis via toll-like receptor 4 and extracellular signal-regulated kinase pathway. J Biol Chem.

[94] Choi SM, Tucker DF, Gross DN, Easton RM, DiPilato LM, Dean AS, Monks BR, Birnbaum MJ: Insulin regulates adipocyte lipolysis via an Akt-independent signaling

[95] Qiao L, Kinney B, Schaack J, Shao J: Adiponectin inhibits lipolysis in mouse adipocytes.

[96] W. Khovidhunkit, R.A. Memon, K.R. Feingold, C. Grunfeld, Infection and inflammation-induced proatherogenic changes of lipoproteins, J. Infect.Dis. 181 (2000)

[97] Davidsson P, Hulthe J, Fagerberg B, Camejo G. Proteomics of apolipoproteins and associated proteins from plasma high-density lipoproteins. Arterioscler Thromb Vasc

[98] Gordon,S.M. et al.:Proteomic characterization of human plasma high density lipoprotein fractionated by gel filtration chromatography. 2010:J. Proteome.Res. 9, 5239–

[99] Gordon S, Deng J, Lu LJ, Davidson WS: High-density lipoprotein proteomics: Identifying new drug targets and biomarkers by understanding functionality. Curr.

[100] Murphy,A.J. et al. High-density lipoprotein reduces the human monocyte inflammatory response. Arterioscler. Thromb. Vasc. Biol. 2008;28, 2071–2077. [101] Gordon SM, Hofmann S, Askew DS, Davidson WS: High density lipoprotein: it's not

[102] Säemann MD, Poglitsch M, Kopecky C, Haidinger M, Hörl WH, Weichhart T:The versatility of HDL: a crucial anti-inflammatory regulator. Eur J Clin Invest. 2010

[103] Galbois A, Thabut D, Tazi KA, Rudler M, Mohammadi MS, Bonnefont- Rousselot D et al: Ex vivo effects of high-density lipoprotein exposure on the lipopolysaccharideinduced inflammatory response in patients with severe cirrhosis. Hepatology

just about lipid transport anymore. Trends Endocrinol Metab. 2011;22:9-15.

11.

9;582(1):117-31.

462–472.80

5249 68.

;40(12):1131-43.

2009;49:175–84.

Biol 2010;30:156–63.

Cardio.RiskRep. 2010:4, 1–8.

Biochem. Funct. 2009;27:407–416.

Endocrinol. 2009 Jan;42(1):57-66.

Diabetes. 2011 May;60(5):1519-27.

pathway. Mol Cell Biol. 2010 Nov;30(21):5009-20.

2009 Feb 27;284(9):5915-26.


[88] Lampidonis AD, Rogdakis E, Voutsinas GE, Stravopodis DJ: The resurgence of Hormone-Sensitive Lipase (HSL) in mammalian lipolysis. Gene. 2011 May 15;477(1-2):1- 11.

352 Lipid Metabolism

Rev 86: 465–514, 2006.

2007;115:2540–2548.

Aug;30(8):1542-9.

Jan;50(1):14-27.

May;42(5):555-9.

Lipid Res. 2009;48:275-97.

Chem. 2010 Dec 24; 285(52):40409-15.

immunity. Nature Rev. Immunol. 2006;6,44–55.

Res Clin Endocrinol Metab. 2005;19:471-82.

triglyceride lipase. Science. 2006 May 5;312(5774):734-7.

activated nuclear receptors. Nature. 2008 Jul 24;454(7203):470-7.

(PPAR gamma) and sepsis. Arch Immunol Ther Exp 2007; 55:19-25.

578, 2004.

[70] Lee J, Kemper JK: Controlling SIRT1 expression by microRNAs in health and metabolic

[71] Tabuchi T, Satoh M, Itoh T, Nakamura M: MicroRNA-34a regulates the longevityassociated protein SIRT1 in coronary artery disease: effect of statins on SIRT1 and

[72] Lopaschuk GD, Ussher JR, Folmes CD, Jaswal JS, Stanley WC. Myocardial fatty acid

[73] Desvergne B, Michalik L, Wahli W: Transcriptional regulation of metabolism. Physiol

[74] Huss JM, Kelly DP: Nuclear receptor signaling and cardiac energetics. Circ Res 95: 568–

[75] Schupp M, Lazar MA: Endogenous ligands for nuclear receptors: digging deeper. J Biol

[76] Grimaldi PA: Metabolic and nonmetabolic regulatory functions of peroxisome proliferator-activated receptor beta. Curr Opin Lipidol. 2010 Jun;21(3):186-91. [77] Finck BN, Kelly DP. Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) regulatory cascade in cardiac physiology and disease. Circulation

[78] Huang W, Glass CK: Nuclear receptors and inflammation control: molecular mechanisms and pathophysiological relevance. Arterioscler Thromb Vasc Biol. 2010

[79] Glass CK, Ogawa S: Combinatorial roles of nuclear receptors in inflammation and

[80] Bensinger SJ, Tontonoz P: Integration of metabolism and inflammation by lipid-

[81] von Knethen A, Soller M, Brüne B: Peroxisome proliferator-activated receptor gamma

[82] Eichner LJ, Giguère V: Estrogen related receptors (ERRs): a new dawn in transcriptional control of mitochondrial gene networks. Mitochondrion. 2011 Jul;11(4):544-52. [83] Arner P: Human fat cell lipolysis: biochemistry, regulation and clinical role. Best Pract

[84] Lass A, Zimmermann R, Oberer M, Zechner R: Lipolysis - a highly regulated multienzyme complex mediates the catabolism of cellular fat stores. Prog Lipid Res. 2011

[85] Ahmadian M, Wang Y, SulHS: Lipolysis in adipocytes. Int J Biochem Cell Biol. 2010

[86] Lafontan M, Langin D: Lipolysis and lipid mobilization in human adipose tissue. Prog

[87] Haemmerle G, Lass A, Zimmermann R, Gorkiewicz G, Meyer C, Rozman J, Heldmaier G, Maier R, Theussl C, Eder S, Kratky D, Wagner EF, Klingenspor M, Hoefler G, Zechner R: Defective lipolysis and altered energy metabolism in mice lacking adipose

microRNA-34a expression. Clin Sci (Lond). 2012 Aug 1;123(3):161-71.

metabolism in health and disease. Physiol Rev. 2010 Jan;90(1):207-58.

disease. Aging (Albany NY). 2010 Aug;2(8):527-34.


[104] Hima Bindu G, Rao VS, Kakkar VV: Friend Turns Foe: Transformation of Anti-Inflammatory HDL to Proinflammatory HDL during Acute-Phase Response. Cholesterol, vol. 2011, no. 19, Article ID 274629, 6 pages, 2011.

The Role of Altered Lipid Metabolism in Septic Myocardial Dysfunction 355

[120] Feingold KR, Moser A, Patzek SM, Shigenaga JK, Grunfeld C: Infection decreases fatty acid oxidation and nuclear hormone receptors in the diaphragm. J Lipid Res.

[121] Maitra U, Chang S, Singh N, Li L: Molecular mechanism underlying the suppression

[122] Halestrap AP: What is the mitochondrial permeability transition pore? J Mol Cell

[123] Andrews DT, Royse C, Royse AG: The mitochondrial permeability transition pore and its role in anaesthesia-triggered cellular protection during ischaemia-reperfusion injury.

[124] Larche J, Lancel S, Hassoun SM, Favory R, Decoster B, Marchetti P, Chopin C, Neviere R: Inhibition of mitochondrial permeability transition prevents sepsis-induced myocardial dysfunction and mortality. J Am Coll Cardiol. 2006 Jul 18;48(2):377-85. [125] Lee J, Giordano S, Zhang J: Autophagy, mitochondria and oxidative stress: cross-talk

[126] Nakahira K, Haspel JA, Rathinam VA, Lee SJ, Dolinay T, Lam HC, Englert JA, Rabinovitch M, Cernadas M, Kim HP, Fitzgerald KA, Ryter SW, Choi AM: Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. Nat Immunol. 2011 Mar;12(3):222-30. [127] Ventura-Clapier R, Garnier A, Veksler V: Transcriptional control of mitochondrial biogenesis: the central role of PGC-1alpha. Cardiovasc Res. 2008 Jul 15;79(2):208-17. [128] Scarpulla RC: Metabolic control of mitochondrial biogenesis through the PGC-1 family

[129] Scarpulla RC: Transcriptional paradigms in mammalian mitochondrial biogenesis and

[130] Vats D, Mukundan L, Odegaard JI, Zhang L, Smith KL, Morel CR, et al. Oxidative metabolism and PGC-1beta attenuate macrophage-mediated inflammation. Cell Metab:

[131] Lin J, Wu P-H, Tarr PT, Lindenberg KS, St-Pierre J,Zhang C-Y, Mootha VK, Jãger S, Vianna, CR, Reznick, R.M., et al. 2004. Defects in adaptive energy metabolism with

[132] Leone, T.C., Lehman, J.J., Finck, B.N., Schaeffer, P.J., Wende, A.R., Boudina, S., Courtois, M., Wozniak, D.F., Sambandam, N., Bernal-Mizrachi, C., et al. PGC-1 deficient mice exhibit multi-system energy metabolic derangements: Muscle dysfunction,

[133] Lai L, Leone TC, Zechner C, Schaeffer PJ, Kelly SM, Flanagan DP, Medeiros DM, Kovacs A, Kelly DP: Transcriptional coactivators PGC-1alpha and PGC-lbeta control overlapping programs required for perinatal maturation of the heart. Genes Dev. 2008

[134] Rimbaud S, Garnier A, Ventura-Clapier R. Mitochondrial biogenesis in cardiac

abnormal weight control, and hepatic steatosis. PLoS Biol. 2005 3: 672–687.

of lipid oxidation during endotoxemia. Mol Immunol. 2009;47:420-5.

2009;50:2055-63.

2006;4:13–24.

Jul 15;22(14):1948-61.

Cardiol. 2009 Jun;46(6):821-31.

Anaesth Intensive Care. 2012 Jan;40(1):46-70.

function. Physiol Rev. 2008 Apr;88(2):611-38.

and redox signalling. Biochem J. 2012 Jan 15;441(2):523-40.

regulatory network. Biochim Biophys Acta. 2011 Jul;1813(7):1269-78.

CNS-linked hyperactivity in PGC-1 null mice. Cell119: 121–135.

pathophysiology. Pharmacol Rep. 2009;61:131-138.


[120] Feingold KR, Moser A, Patzek SM, Shigenaga JK, Grunfeld C: Infection decreases fatty acid oxidation and nuclear hormone receptors in the diaphragm. J Lipid Res. 2009;50:2055-63.

354 Lipid Metabolism

126 51.

Oct;4(5):399-404.

[104] Hima Bindu G, Rao VS, Kakkar VV: Friend Turns Foe: Transformation of Anti-Inflammatory HDL to Proinflammatory HDL during Acute-Phase Response.

[105] Esteve E, Ricart W, Fernández-Real JM: Dyslipidemia and inflammation: an

[106] Khovidhunkit W, Kim MS, Memon RA, Shigenaga JK, Moser AH, Feingold KR, Grunfeld C: Effects of infection and inflammation on lipid and lipoprotein metabolism:

[107] Zhu X, Lee JY, Timmins JM, Brown JM, Boudyguina E, Mulya A et al: Increased cellular free cholesterol in macrophage-specific Abca1 knock-out mice enhances pro-

[108] Murch O, Collin M, Hinds CJ, Thiemermann C: Lipoproteins in inflammation and

[109] Wendel M, Paul R, Heller AR: Lipoproteins in inflammation and sepsis. II. Clinical

[110] Mineo C, Shaul PW: HDL stimulation of endothelial nitric oxide synthase: a novel

[111] Theilmeier,G. et al. (2006) High-density lipoproteins and their constituent, sphingosine-1-phosphate, directly protect the heart against ischemia/reperfusion injury

[112] Frias MA., Lang U, Gerber-Wicht C, James RW: Native and reconstituted HDL protect cardiomyocytes from doxorubicin-induced apoptosis. Cardiovasc. Res. (2010):85, 118–

[113] Frias MA, Lang U, Gerber-Wicht C, James RW: Emerging high-density lipoprotein infusion therapies: fulfilling the promise of epidemiology? J Clin Lipidol. 2010 Sep-

[114] Chien JY, Jerng JS, Yu CJ, Yang PC: Low serum level of high-density lipoprotein is a

[115] Feingold KR, Grunfeld C: The acute phase response inhibits reverse cholesterol

[116] Baranova I, Vishnyakova T, Bocharov A, Chen Z, Remaley AT, Stonik J, Eggerman TL, Patterson AP: Lipopolysaccharide down regulates both scavenger receptor B1 and ATP binding cassette transporter A1 in RAW cells. Infect Immun. 2002 Jun;70(6):2995-3003. [117] Ziouzenkova O, Perrey S, Asatryan L, Hwang J, MacNaul KL, Moller DE, Rader DJ, Sevanian A, Zechner R, Hoefler G, Plutzky J: Lipolysis of triglyceride-rich lipoproteins generates PPAR ligands: evidence for an antiinflammatory role for lipoprotein lipase.

[118] Feingold K, Kim MS, Shigenaga J, Moser A, Grunfeld C: Altered expression of nuclear hormone receptors and coactivators in mouse heart during the acute-phase response.

[119] Feingold KR, Wang Y, Moser A, Shigenaga JK, Grunfeld C: LPS decreases fatty acid oxidation and nuclear hormone receptors in the kidney. J Lipid Res.2008; 49:2179-87.

mechanism of HDL action. Trends Cardiovasc Med. 2003 Aug;13(6):226-31.

in vivo via the S1P3 lysophospholipid receptor. Circulation 114,1403–1409.

poor prognostic factor for severe sepsis. 2005 Crit Care Med 33:1688–1693.

transport. J Lipid Res. 2010 Apr;51(4):682-4. Epub 2010 Jan 13.

Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2730-5

Am J Physiol Endocrinol Metab. 2004;286(2):E201-7.

Cholesterol, vol. 2011, no. 19, Article ID 274629, 6 pages, 2011.

sepsis. I. Basic science. Intensive Care Med. 2007;33:13-24.

aspects. Intensive Care Med. 2007 Jan;33(1):25-35.

evolutionary conserved mechanism. Clin Nutr. 2005 Feb;24(1):16-31.

mechanisms and consequences to the host. J Lipid Res 45 : 1169 –1196,2004.

inflammatory response of macrophages. J Biol Chem 2008;283:22930–41.


[135] Lee IH, Cao L, Mostoslavsky R, Lombard DB, Liu J, Bruns NE, Tsokos M, Alt FW, Finkel T: A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy. Proc. Natl Acad. Sci. USA 105, 3374–3379 (2008).

The Role of Altered Lipid Metabolism in Septic Myocardial Dysfunction 357

[154] Pun PB, Lu J, Kan EM, Moochhala S: Gases in the mitochondria. Mitochondrion: 2010

[155] Cooper CE, Brown GC: The inhibition of mitochondrial cytochrome oxidase by the gases carbon monoxide, nitric oxide, hydrogen cyanide and hydrogen sulfide: chemical mechanism and physiological significance. J Bioenerg Biomembr. 2008 Oct;40(5):533-9. [156] Blackstone E, Morrison M, Roth MB: H2S induces a suspended animation-like state in

[157] Nystul TG, Roth MB: Carbon monoxide-induced suspended animation protects against hypoxic damage in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 2004 Jun

[158] Aslami H, Juffermans NP: Induction of a hypometabolic state during critical illness - a

[159] Baumgart K, Radermacher P, Wagner F: Applying gases for microcirculatory and cellular oxygenation in sepsis: effects of nitric oxide, carbon monoxide, and hydrogen

[160] Zegdi R, Perrin D, Burdin M, Boiteau R, Tenaillon A. Increased endogenous carbon

[161] Hoetzel A, Dolinay T, Schmidt R, Choi AM, Ryter SW: Carbon monoxide in sepsis.

[162] Hui Y, Du J, Tang C, Bin G, Jiang H: Changes in arterial hydrogen sulfide (H2S) content during septic shock and endotoxin shock in rats. J Infect. 2003 Aug;47(2):155-60. [163] Schilling J, Lai L, Sambandam N, Dey CE, Leone TC, Kelly DP. Toll-like receptormediated inflammatory signaling reprograms cardiac energy metabolism by repressing peroxisome proliferator-activated receptor coactivator- 1 signaling. Circ Heart Fail.

[164] Smeding : Salutary effect of resveratrol on sepsis-induced myocardial depression. Crit

[165] Schrauwen P, Schrauwen-Hinderling V, Hoeks J, Hesselink MK. Mitochondrial

[166] Zhang Z, Lowry SF, Guarente L, Haimovich B: Roles of SIRT1 in the acute and restorative phases following induction of inflammation. J Biol Chem. 2010 Dec

[167] Menconi MJ, Arany ZP, Alamdari N, Aversa Z, Gonnella P, O'Neal P, Smith IJ, Tizio S, Hasselgren PO: Sepsis and glucocorticoids downregulate the expression of the nuclear cofactor PGC-1beta in skeletal muscle. Am J Physiol Endocrinol Metab. 2010

[168] Soriano FG, Nogueira AC, Caldini EG, Lins MH, Teixeira AC, Cappi SB, Lotufo PA, Bernik MM, Zsengellér Z, Chen M, Szabó C: Potential role of poly(adenosine 5' diphosphate-ribose) polymerase activation in the pathogenesis of myocardial contractile dysfunction associated with human septic shock. Crit Care Med. 2006

dysfunction and lipotoxicity. Biochim Biophys Acta. 2010;1801:266–271.

monoxide production in severe sepsis. Intensive Care Med. 2002;28:793–796.

Mar;10(2):83-93.

15;101(24):9133-6.

2011;4:474–482.

Care Med. 2012

31;285(53):41391-401.

Oct;299(4):E533-43.

Apr;34(4):1073-9.

mice. Science 2005 Apr 22;308(5721):518.

new concept in the ICU? Neth J Med. 2010 May;68(5):190-8.

sulfide. Curr Opin Anaesthesiol. 2009 Apr;22(2):168-76.

Antioxid Redox Signal. 2007 Nov;9(11):2013-26


[154] Pun PB, Lu J, Kan EM, Moochhala S: Gases in the mitochondria. Mitochondrion: 2010 Mar;10(2):83-93.

356 Lipid Metabolism

[135] Lee IH, Cao L, Mostoslavsky R, Lombard DB, Liu J, Bruns NE, Tsokos M, Alt FW, Finkel T: A role for the NAD-dependent deacetylase Sirt1 in the regulation of

[136] Schumer W, Das Gupta TK, Moss GS, Nyhus LM: Effect of endotoxemia on liver cell

[137] Mela L, Bacalzo LV Jr, Miller LD: Defective oxidative metabolism of rat liver mitochondria in hemorrhagic and endotoxin shock. Am J Physiol. 1971; 220:571-7. [138] Exline MC, Crouser ED: Mitochondrial mechanisms of sepsis-induced organ failure.

[139] Singer M: Mitochondrial function in sepsis: Acute phase versus multiple organ failure.

[140] Smeding L, Plötz FB, Groeneveld AB, Kneyber MC: Structural changes of the heart

[141] Suliman HB, Welty-Wolf KE, Carraway M, Tatro L, Piantadosi CA: Lipopolysaccharide induces oxidative cardiac mitochondrial damage and biogenesis.

[142] Levy RJ, Piel DA, Acton PD, Zhou R, Ferrari VA, Karp JS, Deutschman CS: Evidence of myocardial hibernation in the septic heart. Crit Care Med 33:2752Y2756, 2005. [143] Brealey D, Brand M, Hargreaves I, Heales S, Land J, Smolenski R, Davies NA, Cooper CE, Singer M: Association between mitochondrial dysfunction and severity and

[144] Carré JE, Orban JC, Re L, Felsmann K, Iffert W, Bauer M, Suliman HB, Piantadosi CA, Mayhew TM, Breen P, Stotz M, Singer M: Survival in critical illness is associated with early activation of mitochondrial biogenesis. Am J Respir Crit Care Med. 2010 Sep

[145] Singer M, De Santis V, Vitale D, Jeffcoate W: Multiorgan failure is an adaptive, endocrine-mediated, metabolic response to overwhelming systemic inflammation.

[146] Levy RJ: Mitochondrial dysfunction, bioenergetic impairment and metabolic down-

[147] Azevedo LC: Mitochondrial dysfunction during sepsis. Endocr Metab Immune Disord

[148] Dyson A, Stidwill R, Taylor V, Singer M: Tissue oxygen monitoring in rodent models

[149] Fink MP: Bench-to-bedside review: Cytopathic hypoxia. Critical Care 2002;6:491–499. [150] Kato K, Giulivi C: Critical overview of mitochondrial nitric-oxide synthase. Front

[151] Valdez LB, Boveris A: Mitochondrial nitric oxide synthase, a voltage-dependent enzyme, is responsible for nitric oxide diffusion to cytosol. Front Biosci 2007; 12:1210-9. [152] Bateman RM, Sharpe MD, Goldman D, Lidington D, Ellis CG: Inhibiting nitric oxide overproduction during hypotensive sepsis increases local oxygen consumption in rat

of shock. Am J Physiol Heart Circ Physiol. 2007 Jul;293(1):H526-33.

[153] Brown GC: Nitric oxide and mitochondria. Front Biosci. 2007; 12:1024-33.

autophagy. Proc. Natl Acad. Sci. USA 105, 3374–3379 (2008).

mitochondria in man. Ann Surg. 1970 ; 171:875-82.

Mitochondria in Sepsis. Front Biosci. 2008 ;13:5030-41.

during severe sepsis or septic shock. Shock. 2012 May;37(5):449-56.

outcome of septic shock. Lancet. 2002 Jul 20;360(9328):219-23.

Crit Care Med 2007; 35[Suppl.]:S441–S448.

Cardiovasc Res 64:279Y288, 2004.

15;182(6):745-51.

Lancet 2004; 364:545-8.

Biosci. 2006 ; 11:2725-38.

regulation in sepsis. Shock 2007; 28:24-28.

skeletal muscle. Crit Care Med 2008; 36:225-23.

Drug Targets. 2010 Sep;10(3):214-23.


[169] Pacher P, Szabó C: Role of poly(ADP-ribose) polymerase 1 (PARP-1) in cardiovascular diseases: the therapeutic potential of PARP inhibitors. Cardiovasc Drug Rev. 2007 Fall;25(3):235-60.

The Role of Altered Lipid Metabolism in Septic Myocardial Dysfunction 359

[184] G Redl , P Germann , H Plattner e Al: Right ventricular function in early septic shock

[185] Bouhemad B, Nicolas-Robin A, Arbelot C, Arthaud M, Féger F, Rouby JJ: Acute left ventricular dilatation and shock-induced myocardial dysfunction. Crit Care Med 2009,

[186] J Poelaert, C Declerck, D Vogelaers e Al: Left ventricular systolic and diastolic function

[187] Vieillard Baron A, Schmitt JM, Beauchet A et Al: Early preload adaptation in septic shock? A transesophageal echocardiographic study. Anesthesiology 2001;94:400–6. [188] Vieillard-Baron A: Septic cardiomyopathy. Ann Intensive Care. 2011 Apr 13;1(1):6. [189] Suffredini A, Fromm RE, Parker MM, Brenner M, Kovacs JA, Wesley RA,Parrillo JE: The cardiovascular response of normal humans to the administration of endotoxin. N

[190] Vieillard-Baron A, Caille V, Charron C, et al. Actual incidence of global left ventricular

[191] Vincent JL, Reuse C, Frank N, Contempré B, Kahn RJ: Right ventricular dysfunction in septic shock: assessment by measurements of right ventricular ejection fraction using

[192] Etchecopar-Chevreuil C, François B, Clavel M, Pichon N, Gastinne H, Vignon P: Cardiac morphological and functional changes during early septic shock: a

[194] Parrillo JE, Burch C, Shelhamer JH, Parker MM, Natanson C, Schuette W: A circulating myocardial depressant substance in humans with septic shock. Septic shock patients with a reduced ejection fraction have a circulating factor that depresses in vitro

[195] Kumar A, Thota V, Dee L, Olson J, Uretz E, Parrillo JE: Tumor necrosis factor alpha and interleukin 1beta are responsible for in vitro myocardial cell depression induced by

[196] Flynn A, Chokkalingam Mani B, Mather PJ: Sepsis-induced cardiomyopathy: a review

[197] Marchant DJ, Boyd JH, Lin DC, Granville DJ, Garmaroudi FS, McManus BM:

[198] Fallach R, Shainberg A, Avlas O, Fainblut M, Chepurko Y, Porat E, Hochhauser E: Cardiomyocyte Toll-like receptor 4 is involved in heart dysfunction following septic

[199] Zou L, Feng Y, Chen YJ, Si R, Shen S, Zhou Q, Ichinose F, Scherrer-Crosbie M, Chao W: Toll-like receptor 2 plays a critical role in cardiac dysfunction during polymicrobial

transesophageal echocardiographic study. Intensive Care Med 2008, 34: 250-256. [193] Jianhui L, Rosenblatt-Velin N, Loukili N, Pacher P, Feihl F, Waeber B, Liaudet L: Endotoxin impairs cardiac hemodynamics by affecting loading conditions but not by reducing cardiac inotropism. Am J Physiol Heart Circ Physiol. 2010 Aug;299(2):H492- 501.192)Wiggers CJ. Myocardial depression in shock: a survey of cardiodynamic

hypokinesia in adult septic shock. Crit Care Med 2008; 36:1701–1706.

thermodilution technique. Acta Anaesthesiol Scand 1989, 33: 34-38.

myocardial cell performance. J Clin Invest. 1985 Oct;76(4):1539-53.

of pathophysiologic mechanisms. Heart Fail Rev. 2010 Nov;15(6):605-11.

Inflammation in myocardial diseases. Circ Res. 2012 Jan 6;110(1):126-44.

shock or myocardial ischemia. J Mol Cell Cardiol. 2010 Jun;48(6):1236-44.

human septic shock serum. J Exp Med 183(3):949Y958, 1996.

sepsis. Crit Care Med. 2010 May;38(5):1335-42.

states. Intensive Care Med 1993;19:3–7.

Engl J Med 1989, 321: 280-287.

studies. Am Heart J. 1947;33:633– 650.

in septic shock. Intensive Care Med 1997;23:553–60.

37: 441-447.


[184] G Redl , P Germann , H Plattner e Al: Right ventricular function in early septic shock states. Intensive Care Med 1993;19:3–7.

358 Lipid Metabolism

Fall;25(3):235-60.

1;47(11):1517-25.

2008 Apr;29(4):497-503.

Intern Med 1984;/100:/483 90.

27:10-18.

[169] Pacher P, Szabó C: Role of poly(ADP-ribose) polymerase 1 (PARP-1) in cardiovascular diseases: the therapeutic potential of PARP inhibitors. Cardiovasc Drug Rev. 2007

[170] Melvin RG, Andrews MT: Torpor induction in mammals: recent discoveries fueling

[171] Liu TF, Brown CM, El Gazzar M, McPhail L, Millet P, Rao A, Vachharajani VT, Yoza BK, McCall CE: Fueling the flame: bioenergy couples metabolism and inflammation. J

[172] Liu TF, Yoza BK, El Gazzar M, Vachharajani VT, McCall CE: NAD+-dependent SIRT1 deacetylase participates in epigenetic reprogramming during endotoxin tolerance. J Biol

[173] Dare AJ, Phillips AR, Hickey AJ, Mittal A, Loveday B, Thompson N, Windsor JA: A systematic review of experimental treatments for mitochondrial dysfunction in sepsis and multiple organ dysfunction syndrome. Free Radic Biol Med. 2009 Dec

[174] Ruggieri AJ, Levy RJ, Deutschman CS: Mitochondrial dysfunction and resuscitation in

[175] Protti A, Singer M: Bench-to-bedside review: potential strategies to protect or reverse mitochondrial dysfunction in sepsis-induced organ failure. Crit Care. 2006;10(5):228. [176] Kozlov AV, Bahrami S, Calzia E, Dungel P, Gille L, Kuznetsov AV, Troppmair J: Mitochondrial dysfunction and biogenesis: do ICU patients die from mitochondrial

[177] Lancel S, Joulin O, Favory R, Goossens JF, Kluza J, Chopin C, Formstecher P, Marchetti P, Neviere R: Ventricular myocyte caspases are directly responsible for endotoxin-

[178] Buerke U, Carter JM, Schlitt A, Russ M, Schmidt H, Sibelius U, Grandel U, Grimminger F, Seeger W, Mueller-Werdan U, Werdan K, Buerke M: Apoptosis contributes to septic cardiomyopathy and is improved by simvastatin therapy. Shock.

[179] Balija TM, Lowry SF: Lipopolysaccharide and sepsis-associated myocardial

[180] Rossi MA, Celes MR, Prado CM: Myocardial structural changes in long term human severe sepsis\septic shock may be responsible for cardiac dysfunction. Shock 2007;

[181] Celes MR, Torres-Duenas D, Prado CM, et al. Increased sarcolemmal permeability as an early event in experimental septic cardiomyopathy: a potential role for oxidative

[182] Celes MR, Torres-Duenas D, Malvestio LM, et al. Disruption of sarcolemmal dystrophin and beta-dystroglycan may be a potential mechanism for myocardial

[183] Parker MM, Shelhamer JH, Bacharach SL, Green MV, Natanson C, Frederick TM, et al: Profound but reversible myocardial depression in patients with septic shock. Ann

induced cardiac dysfunction. Circulation. 2005 May 24;111(20):2596-604.

new ideas. Trends Endocrinol Metab. 2009 Dec;20(10):490-8.

Leukoc Biol. 2012 May 9. [Epub ahead of print].

sepsis. Crit Care Clin. 2010 Jul;26(3):567-75, x-xi.

failure? Ann Intensive Care. 2011 Sep 26;1(1):41.

dysfunction. Curr Opin Infect Dis. 2011 Jun;24(3):248-53.

damage to lipids and proteins. Shock 2010; 33:322–331.

dysfunction in severe sepsis. Lab Invest 2010; 90:531–542.

Chem. 2011 Mar 18;286(11):9856-64.


[200] Gao M, Ha T, Zhang X, Liu L, Wang X, Kelley J, Singh K, Kao R, Gao X, Williams D, Li C: Toll-like receptor 3 plays a central role in cardiac dysfunction during polymicrobial sepsis. Crit Care Med. 2012 May 24. [Epub ahead of print] J. [200] Rolli, N. Rosenblatt-Velin, J. Li et al: "Bacterial flagellin triggers cardiac innate immune responses and acute contractile dysfunction,". PLoS ONE, vol. 5, no. 9, Article ID e12687, 1–13, 2010.

The Role of Altered Lipid Metabolism in Septic Myocardial Dysfunction 361

[216] Neubauer S, Horn M, Cramer M, et al: Myocardial phosphocreatine-to-ATP ratio is a predictor of mortality in patients with dilated cardiomyopathy. Circulation

[217] Neubauer S, Horn M, Pabst T, et al: Contributions of 31P-magnetic resonance spectroscopy to the understanding of dilated heart muscle disease. Eur Heart J

[218] Sack MN, Rader TA, Park S, Bastin J, McCune SA, Kelly DP: Fatty acid oxidation enzyme gene expression is downregulated in the failing heart. Circulation. 1996 Dec

[219] Sihag S, Cresci S, Li AY, Sucharov CC, Lehman JJ. PGC-1alpha and ERRalpha target gene downregulation is a signature of the failing human heart. J Mol Cell Cardiol 46:

[220] Abel ED, Doenst T: Mitochondrial adaptations to physiological vs. pathological

[221] Lehman JJ, Barger PM, Kovacs A, Saffitz JE, Medeiros DM, Kelly DP: Peroxisome proliferator-activated receptor gamma coactivator-1 promotes cardiac mitochondrial

[222] L. K. Russell, C. M. Mansfield, J. J. Lehman, et al., "Cardiac specific induction of the transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator-1α promotes mitochondrial biogenesis and reversible cardiomyopathy in a developmental

[223] Leone TC, Lehman JJ, FinckBN et al: "PGC-1α deficiency causes multi-system energy metabolic derangements: muscle dysfunction, abnormal weight control and hepatic

[224] Thum T, Galuppo P, Wolf C, Fiedler J, Kneitz S, van Laake LW, Doevendans PA, Mummery CL, Borlak J, Haverich A, Gross C, Engelhardt S, Ertl G, Bauersachs J: MicroRNAs in the human heart: a clue to fetal gene reprogramming in heart failure.

[225] Sucharov C, Bristow MR, Port JD: miRNA expression in the failing human heart:

[226] Divakaran V, Mann DL: The emerging role of microRNAs in cardiac remodeling and

[227] Molnár A, Tóth A, Bagi Z, Papp Z, Edes I, Vaszily M, Galajda Z, Papp JG, Varró A, Szüts V, Lacza Z, Gerö D, Szabó C: Activation of the poly(ADP-ribose) polymerase

[228] Sundaresan NR, Pillai VB, Gupta MP: Emerging roles of SIRT1 deacetylase in regulating cardiomyocyte survival and hypertrophy. J Mol Cell Cardiol. 2011

[229] Rajamohan SB, Pillai VB, Gupta M, Sundaresan NR, Birukov KG, Samant S, Hottiger MO, Gupta MP: SIRT1 promotes cell survival under stress by deacetylation-dependent deactivation of poly(ADP-ribose) polymerase 1. Mol Cell Biol. 2009 Aug;29(15):4116-29. [230] Virchow R. Cellular Pathology as Based Upon Physiological and Pathological

cardiac hypertrophy. Cardiovasc Res. 2011 May 1;90(2):234-42.

stage-dependent manner," Circulation Research 2004; 94: 525–533.

functional correlates. J Mol Cell Cardiol. 2008 Aug;45(2):185-92.

pathway in human heart failure. Mol Med. 2006 Jul-Aug;12(7-8):143-52.

biogenesis. J Clin Invest. 2000;106:847–856.

steatosis," PLoS Biology, vol. 3, no. 4, p. e101, 2005.

heart failure. Circ Res. 2008 Nov 7;103(10):1072-83.

Histology. London: John Churchill, 1860:325.

Circulation. 2007 Jul 17;116(3):258-67.

1997;96:2190-6.

1;94(11):2837-42.

201–212, 2009.

Oct;51(4):614-8.

1995;16:Suppl O:115-8.


[216] Neubauer S, Horn M, Cramer M, et al: Myocardial phosphocreatine-to-ATP ratio is a predictor of mortality in patients with dilated cardiomyopathy. Circulation 1997;96:2190-6.

360 Lipid Metabolism

416, 2001.

Apr;7(2):225-32.

May;129:1349-66.

15;356(11):1140-5.1.

Pharmacol. 2009;874:252-65.

[200] Gao M, Ha T, Zhang X, Liu L, Wang X, Kelley J, Singh K, Kao R, Gao X, Williams D, Li C: Toll-like receptor 3 plays a central role in cardiac dysfunction during polymicrobial sepsis. Crit Care Med. 2012 May 24. [Epub ahead of print] J. [200] Rolli, N. Rosenblatt-Velin, J. Li et al: "Bacterial flagellin triggers cardiac innate immune responses and acute

contractile dysfunction,". PLoS ONE, vol. 5, no. 9, Article ID e12687, 1–13, 2010. [201] Boyd JH, Kan B, Roberts H, Wang Y, Walley KR. S100a8 and s100a9 mediate endotoxin-induced cardiomyocyte dysfunction via the receptor for advanced glycation

[202] Zhang Z, Schluesener HJ: Mammalian toll-like receptors: from endogenous ligands to

[203] SP Jones, R Bolli: The ubiquitous role of nitric oxide in cardioprotection Journal of

[206] Tavernier B, Li JM, El-Omar MM, Lanone S, Yang ZK, Trayer IP, Mebazaa A, Shah AM: Cardiac contractility impairment associated with increased phosphorylation of

[207] Hassoun SM, Marechal X, Montaigne D, et al. Prevention of endotoxin-induced sarcoplasmic reticulum calcium leak improves mitochondrial and myocardial

[208] Lehnart SE: Novel targets for treating heart and muscle disease: stabilizing ryanodine receptors and preventing intracellular calcium leak. Curr Opin Pharmacol. 2007

[209] Huang J, Wang Y, Jiang D, Zhou J, Huang X: The sympathetic-vagal balance against

[210] Slezak J, Tribulova N, Okruhlicova L, Dhingra R, Bajaj A, Freed D, Singal P: Hibernating myocardium: pathophysiology, diagnosis, and treatment. Can J Physiol

[212] Maeder M, Fehr T, Rickli H e Al: Sepsis-associated myocardial dysfunction: diagnostic and prognostic impact of cardiac troponins and natriuretic peptides. Chest. 2006

[213] McLean AS, Tang B, Nalos M, Huang SJ, Stewart DE: Increased B-type natriuretic peptide (BNP) level is a strong predictor for cardiac dysfunction in intensive care unit

[214] de Bold AJ: Cardiac natriuretic peptides gene expression and secretion in

[215] Neubauer S: The failing heart--an engine out of fuel.N Engl J Med. 2007 Mar

[204] De Backer D: Nitric oxide inhibition in septic shock. Reanimation 2006;15;145-149. [205] LL Wu, C Tang, MS Liu: Altered phosphorylation and calcium sensitivity of cardiac myofibrillar proteins during sepsis . Am J Physiol Regul Integr Comp Physiol 281:408-

end products. Circ Res. 2008;102:1239 –1246.

Molecular Cellul Cardiol 2006;40:16–23.

tissue regeneration. Cell Mol Life Sci. 2006 Dec;63(24):2901-7.

troponin I in endotoxemic rats. Faseb J 2001, 15:294-296.

endotoxemia. J Neural Transm. 2010 Jun;117(6):729-35.

[211] Hunter JD, Doddi M: Sepsis and the heart. Br J Anaesth. 2010;104: 3-11.

dysfunction. Crit Care Med 2008; 36:2590–2596.

patients. Anaesth Intensive Care 2003, 31:21-27.

inflammation. J Investig Med. 2009 Jan;57(1):29-32.


[231] Tontonoz P, Spiegelman BM. Fat and beyond: The diverse biology of PPARgamma. Annu Rev Biochem. 2008;77: 289-312.

**Chapter 15** 

© 2013 Reignault et al., licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,

**Lipids as Markers of Induced Resistance in** 

Natacha Bourdon, Delphine Renard-Merlier and Philippe Reignault

Christine Tayeh, Béatrice Randoux, Frédéric Laruelle,

Additional information is available at the end of the chapter

to existing pathogen control methods [1].

http://dx.doi.org/10.5772/51279

**1. Introduction** 

**Wheat: A Biochemical and Molecular Approach** 

Plant disease resistance can be defined as the ability of the plant to prevent or restrict pathogen growth and multiplication. All plants, whether they are resistant or susceptible, respond to pathogen attack by the induction of a coordinated resistance strategy. Acceleration and/or amplification of the plant responses by the application of resistance inducers could provide a biologically, environmentally and commercially viable alternative

Among pathogenic fungi, the obligate parasite *Blumeria graminis* f. sp. *tritici* (*Bgt*) is responsible for wheat (*Triticum aestivum*) powdery mildew, one of the most damaging foliar diseases of this crop, especially in Northern Europe. Worldwide yield losses due to wheat powdery mildew would be about 30% without chemical treatments, so that an extensive use of conventional fungicides is undertaken. Moreover, populations of *Bgt* resistant to the main chemical fungicides (ergosterol biosynthesis inhibitors, EBIs and 2-aminopyridines) are rising, and these resistant strains emerged all over most European territories [2]. New disease management strategies based on the use of molecules that induce plant resistance *via* the elicitation of defence responses are therefore developed in order to reduce the use of conventional fungicides. These strategies match the growing concern about the

Induced partial resistance against *B. graminis* f.sp. *tritici* has been obtained in wheat with different elicitors and resistance inducers. Infection level was reduced to 57% and 58% relative to controls when nonacetylated and acetylated oligogalacturonides, respectively, were sprayed on wheat 48h before inoculation with *Bgt* [5]. Trehalose, a non-reducing disaccharide found in a wide variety of organisms, confers a 60% protection level against

and reproduction in any medium, provided the original work is properly cited.

consequences of the use of fungicides on both health and environment [3,4].


**Chapter 15** 
