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Erschienen in:

01.03.2011 | Riley Symposium

Autophagy in Cardiac Plasticity and Disease

Erschienen in: Pediatric Cardiology | Ausgabe 3/2011

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Abstract

The heart is a highly plastic organ. In response to the physiological stress of normal life, as well as the pathological stress of disease, the myocardium manifests robust and rapid changes in mass. In the context of disease-associated stress, this myocardial remodeling response can culminate in ventricular thinning, mechanical dysfunction, and a clinical syndrome of heart failure. Recently, autophagy, a process of cellular cannibalization, has been implicated in many of these remodeling reactions. In some settings, the autophagic response is beneficial and pro-survival; in other contexts, it is maladaptive and promotes disease progression. Together, these observations raise the intriguing prospect of targeting maladaptive autophagy and advancing cell survival-promoting, adaptive autophagy to benefit patients with heart disease.

Bergmann O, Bhardwaj RD, Bernard S, Zdunek S, Barnabe-Heider F, Walsh S et al (2009) Evidence for cardiomyocyte renewal in humans. Science 324:98–102PubMedCrossRef

Cao DJ, Wang ZV, Battiprolu PK, Jiang N, Morales C, Kong Y et al (2011) HDAC inhibitors attenuate cardiac hypertrophy by suppressing autophagy. Proc Natl Acad Sci USA (in press)

Chan EY (2009) mTORC1 phosphorylates the ULK1-mAtg13-FIP200 autophagy regulatory complex. Sci Signal 2: pe51

Chen Q, Liu JB, Horak KM, Zheng H, Kumarapeli AR, Li J et al (2005) Intrasarcoplasmic amyloidosis impairs proteolytic function of proteasomes in cardiomyocytes by compromising substrate uptake. Circ Res 97:1018–1026PubMedCrossRef

Dalakas MC, Park KY, Semino-Mora C, Lee HS, Sivakumar K, Goldfarb LG (2000) Desmin myopathy, a skeletal myopathy with cardiomyopathy caused by mutations in the desmin gene. N Engl J Med 342:770–780PubMedCrossRef

Decker RS, Wildenthal K (1980) Lysosomal alterations in hypoxic and reoxygenated hearts. I. Ultrastructural and cytochemical changes. Am J Pathol 98:425–444PubMed

Decker RS, Decker ML, Herring GH, Morton PC, Wildenthal K (1980) Lysosomal vacuolar apparatus of cardiac myocytes in heart of starved and re-fed rabbits. J Mol Cell Cardiol 12:1175–1189PubMedCrossRef

Decker RS, Poole AR, Crie JS, Dingle JT, Wildenthal K (1980) Lysosomal alterations in hypoxic and reoxygenated hearts. II. Immunohistochemical and biochemical changes in cathepsin D. Am J Pathol 98:445–456PubMed

Depre C, Wang Q, Yan L, Hedhli N, Peter P, Chen L et al (2006) Activation of the cardiac proteasome during pressure overload promotes ventricular hypertrophy. Circulation 114:1821–1828PubMedCrossRef

10.

Diwan A, Krenz M, Syed FM, Wansapura J, Ren X, Koesters AG et al (2007) Inhibition of ischemic cardiomyocyte apoptosis through targeted ablation of Bnip3 restrains postinfarction remodeling in mice. J Clin Invest 117:2825–2833PubMedCrossRef

11.

Elsasser A, Vogt AM, Nef H, Kostin S, Mollmann H, Skwara W et al (2004) Human hibernating myocardium is jeopardized by apoptotic and autophagic cell death. J Am Coll Cardiol 43:2191–2199PubMedCrossRef

12.

Frey N, Katus HA, Olson EN, Hill JA (2004) Hypertrophy of the heart: a new therapeutic target? Circulation 109:1580–1589PubMedCrossRef

13.

Gurusamy N, Lekli I, Gorbunov NV, Gherghiceanu M, Popescu LM, Das DK (2009) Cardioprotection by adaptation to ischaemia augments autophagy in association with BAG-1 protein. J Cell Mol Med 13:373–387PubMedCrossRef

14.

Hamacher-Brady A, Brady NR, Gottlieb RA (2006) Enhancing macroautophagy protects against ischemia/reperfusion injury in cardiac myocytes. J Biol Chem 281:29776–29787PubMedCrossRef

15.

Hamacher-Brady A, Brady NR, Logue SE, Sayen MR, Jinno M, Kirshenbaum LA et al (2007) Response to myocardial ischemia/reperfusion injury involves Bnip3 and autophagy. Cell Death Differ 14:146–157PubMedCrossRef

16.

Hein S, Arnon E, Kostin S, Schonburg M, Elsasser A, Polyakova V et al (2003) Progression from compensated hypertrophy to failure in the pressure-overloaded human heart: structural deterioration and compensatory mechanisms. Circulation 107:984–991PubMedCrossRef

17.

Hill JA, Olson EN (2008) Cardiac plasticity. N Engl J Med 358:1370–1380PubMedCrossRef

18.

Hill JA, Karimi M, Kutschke W, Davisson RL, Zimmerman K, Wang Z et al (2000) Cardiac hypertrophy is not a required compensatory response to short-term pressure overload. Circulation 101:2863–2869PubMed

19.

Hudlicka O, Brown M, Egginton S (1992) Angiogenesis in skeletal and cardiac muscle. Physiol Rev 72:369–417PubMed

20.

Inoue Y, Klionsky DJ (2010) Regulation of macroautophagy in Saccharomyces cerevisiae. Semin Cell Dev Biol 21:664–670PubMedCrossRef

21.

Iwata A, Riley BE, Johnston JA, Kopito RR (2005) HDAC6 and microtubules are required for autophagic degradation of aggregated huntingtin. J Biol Chem 280:40282–40292PubMedCrossRef

22.

Izumiya Y, Shiojima I, Sato K, Sawyer DB, Colucci WS, Walsh K (2006) Vascular endothelial growth factor blockade promotes the transition from compensatory cardiac hypertrophy to failure in response to pressure overload. Hypertension 47:887–893PubMedCrossRef

23.

Kamada Y, Funakoshi T, Shintani T, Nagano K, Ohsumi M, Ohsumi Y (2000) Tor-mediated induction of autophagy via an Apg1 protein kinase complex. J Cell Biol 150:1507–1513PubMedCrossRef

24.

Kamada Y, Sekito T, Ohsumi Y (2004) Autophagy in yeast: a TOR-mediated response to nutrient starvation. Curr Top Microbiol Immunol 279:73–84PubMedCrossRef

25.

Kanamori H, Takemura G, Maruyama R, Goto K, Tsujimoto A, Ogino A et al (2009) Functional significance and morphological characterization of starvation-induced autophagy in the adult heart. Am J Pathol 174:1705–1714PubMedCrossRef

26.

Kanki T, Wang K, Cao Y, Baba M, Klionsky DJ (2009) Atg32 is a mitochondrial protein that confers selectivity during mitophagy. Dev Cell 17:98–109PubMedCrossRef

27.

Kim I, Rodriguez-Enriquez S, Lemasters JJ (2007) Selective degradation of mitochondria by mitophagy. Arch Biochem Biophys 462:245–253PubMedCrossRef

28.

Klionsky DJ (2007) Autophagy: from phenomenology to molecular understanding in less than a decade. Nat Rev Mol Cell Biol 8:931–937PubMedCrossRef

29.

Knaapen MW, Davies MJ, De Bie M, Haven AJ, Martinet W, Kockx MM (2001) Apoptotic versus autophagic cell death in heart failure. Cardiovasc Res 51:304–312PubMedCrossRef

30.

Kostin S, Pool L, Elsasser A, Hein S, Drexler HC, Arnon E et al (2003) Myocytes die by multiple mechanisms in failing human hearts. Circ Res 92:715–724PubMedCrossRef

31.

Kundu M, Thompson CB (2008) Autophagy: basic principles and relevance to disease. Annu Rev Pathol 3:427–455PubMedCrossRef

32.

Levine B, Klionsky DJ (2004) Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev Cell 6:463–477PubMedCrossRef

33.

Levine B, Kroemer G (2008) Autophagy in the pathogenesis of disease. Cell 132:27–42PubMedCrossRef

34.

Levine B, Yuan J (2005) Autophagy in cell death: an innocent convict? J Clin Invest 115:2679–2688PubMedCrossRef

35.

Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP (1990) Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med 322:1561–1566PubMedCrossRef

36.

Lockshin RA, Zakeri Z (2002) Caspase-independent cell deaths. Curr Opin Cell Biol 14:727–733PubMedCrossRef

37.

Maloyan A, Sanbe A, Osinska H, Westfall M, Robinson D, Imahashi K et al (2005) Mitochondrial dysfunction and apoptosis underlie the pathogenic process in alpha-B-crystallin desmin-related cardiomyopathy. Circulation 112:3451–3461PubMedCrossRef

38.

Maron BJ, Roberts WC, Arad M, Haas TS, Spirito P, Wright GB et al (2009) Clinical outcome and phenotypic expression in LAMP2 cardiomyopathy. JAMA 301:1253–1259PubMedCrossRef

39.

Martinet W, Knaapen MW, Kockx MM, De Meyer GR (2007) Autophagy in cardiovascular disease. Trends Mol Med 13:482–491PubMedCrossRef

40.

Matsui Y, Takagi H, Qu X, Abdellatif M, Sakoda H, Asano T et al (2007) Distinct roles of autophagy in the heart during ischemia and reperfusion: roles of AMP-activated protein kinase and Beclin 1 in mediating autophagy. Circ Res 100:914–922PubMedCrossRef

41.

Mizushima N (2007) Autophagy: process and function. Genes Dev 21:2861–2873PubMedCrossRef

42.

Mizushima N, Levine B, Cuervo AM, Klionsky DJ (2008) Autophagy fights disease through cellular self-digestion. Nature 451:1069–1075PubMedCrossRef

43.

Nakai A, Yamaguchi O, Takeda T, Higuchi Y, Hikoso S, Taniike M et al (2007) The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress. Nat Med 13:619–624PubMedCrossRef

44.

Nishida K, Kyoi S, Yamaguchi O, Sadoshima J, Otsu K (2009) The role of autophagy in the heart. Cell Death Differ 16:31–38PubMedCrossRef

45.

Nishino I, Fu J, Tanji K, Yamada T, Shimojo S, Koori T et al (2000) Primary LAMP-2 deficiency causes X-linked vacuolar cardiomyopathy and myopathy (Danon disease). Nature 406:906–910PubMedCrossRef

46.

Omary MB, Coulombe PA, McLean WH (2004) Intermediate filament proteins and their associated diseases. N Engl J Med 351:2087–2100PubMedCrossRef

47.

Perng MD, Wen SF, van den IJssel P, Prescott AR, Quinlan RA (2004) Desmin aggregate formation by R120G alphaB-crystallin is caused by altered filament interactions and is dependent upon network status in cells. Mol Biol Cell 15:2335–2346PubMedCrossRef

48.

Pfeifer U, Fohr J, Wilhelm W, Dammrich J (1987) Short-term inhibition of cardiac cellular autophagy by isoproterenol. J Mol Cell Cardiol 19:1179–1184PubMedCrossRef

49.

Rajasekaran NS, Connell P, Christians ES, Yan LJ, Taylor RP, Orosz A et al (2007) Human alpha B-crystallin mutation causes oxido-reductive stress and protein aggregation cardiomyopathy in mice. Cell 130:427–439PubMedCrossRef

50.

Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM et al (2010) Heart disease and stroke statistics―2011 update: a report from the American Heart Association. Circulation

51.

Rothermel BA, Hill JA (2007) Myocyte autophagy in heart disease: friend or foe? Autophagy 3:632–634PubMed

52.

Rothermel BA, Hill JA (2008) Autophagy in load-induced heart disease. Circ Res 103:1363–1369PubMedCrossRef

53.

Sanbe A, Osinska H, Saffitz JE, Glabe CG, Kayed R, Maloyan A et al (2004) Desmin-related cardiomyopathy in transgenic mice: a cardiac amyloidosis. Proc Natl Acad Sci USA 101:10132–10136PubMedCrossRef

54.

Shimomura H, Terasaki F, Hayashi T, Kitaura Y, Isomura T, Suma H (2001) Autophagic degeneration as a possible mechanism of myocardial cell death in dilated cardiomyopathy. Jpn Circ J 65:965–968PubMedCrossRef

55.

Shiojima I, Sato K, Izumiya Y, Schiekofer S, Ito M, Liao R et al (2005) Disruption of coordinated cardiac hypertrophy and angiogenesis contributes to the transition to heart failure. J Clin Invest 115:2108–2118PubMedCrossRef

56.

Tanaka Y, Guhde G, Suter A, Eskelinen EL, Hartmann D, Lullmann-Rauch R et al (2000) Accumulation of autophagic vacuoles and cardiomyopathy in LAMP-2-deficient mice. Nature 406:902–906PubMedCrossRef

57.

Tannous P, Zhu H, Johnstone JL, Shelton JM, Rajasekaran NS, Benjamin IJ et al (2008) Autophagy is an adaptive response in desmin-related cardiomyopathy. Proc Natl Acad Sci USA 105:9745–9750PubMedCrossRef

58.

Tannous P, Zhu H, Nemchenko A, Berry JM, Johnstone JL, Shelton JM et al (2008) Intracellular protein aggregation is a proximal trigger of cardiomyocyte autophagy. Circulation 117:3070–3078PubMedCrossRef

59.

Twig G, Elorza A, Molina AJ, Mohamed H, Wikstrom JD, Walzer G et al (2008) Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J 27:433–446PubMedCrossRef

60.

Valentim L, Laurence KM, Townsend PA, Carroll CJ, Soond S, Scarabelli TM et al (2006) Urocortin inhibits Beclin1-mediated autophagic cell death in cardiac myocytes exposed to ischaemia/reperfusion injury. J Mol Cell Cardiol 40:846–852PubMedCrossRef

61.

Vicart P, Caron A, Guicheney P, Li Z, Prevost MC, Faure A et al (1998) A missense mutation in the alphaB-crystallin chaperone gene causes a desmin-related myopathy. Nat Genet 20:92–95PubMedCrossRef

62.

Wang X, Osinska H, Dorn GW 2nd, Nieman M, Lorenz JN, Gerdes AM et al (2001) Mouse model of desmin-related cardiomyopathy. Circulation 103:2402–2407PubMed

63.

Wang X, Osinska H, Klevitsky R, Gerdes AM, Nieman M, Lorenz J et al (2001) Expression of R120G-alphaB-crystallin causes aberrant desmin and alphaB-crystallin aggregation and cardiomyopathy in mice. Circ Res 89:84–91PubMedCrossRef

64.

Xie Z, Klionsky DJ (2007) Autophagosome formation: core machinery and adaptations. Nat Cell Biol 9:1102–1109PubMedCrossRef

65.

Yamamoto S, Sawada K, Shimomura H, Kawamura K, James TN (2000) On the nature of cell death during remodeling of hypertrophied human myocardium. J Mol Cell Cardiol 32:161–175PubMedCrossRef

66.

Yan L, Vatner DE, Kim SJ, Ge H, Masurekar M, Massover WH et al (2005) Autophagy in chronically ischemic myocardium. Proc Natl Acad Sci USA 102:13807–13812PubMedCrossRef

67.

Yitzhaki S, Huang C, Liu W, Lee Y, Gustafsson AB, Mentzer RM Jr et al (2009) Autophagy is required for preconditioning by the adenosine A1 receptor-selective agonist CCPA. Basic Res Cardiol 104:157–167PubMedCrossRef

68.

Yu L, McPhee CK, Zheng L, Mardones GA, Rong Y, Peng J et al (2010) Termination of autophagy and reformation of lysosomes regulated by mTOR. Nature 465:942–946PubMedCrossRef

69.

Zhang H, Bosch-Marce M, Shimoda LA, Tan YS, Baek JH, Wesley JB et al (2008) Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia. J Biol Chem 283:10892–10903PubMedCrossRef

70.

Zhu H, Tannous P, Johnstone JL, Kong Y, Shelton JM, Richardson JA et al (2007) Cardiac autophagy is a maladaptive response to hemodynamic stress. J Clin Invest 117:1782–1793PubMedCrossRef

Titel: Autophagy in Cardiac Plasticity and Disease
Publikationsdatum: 01.03.2011
Erschienen in: Pediatric Cardiology / Ausgabe 3/2011
Print ISSN: 0172-0643
Elektronische ISSN: 1432-1971
DOI: https://doi.org/10.1007/s00246-010-9883-6

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