© 2000 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
The role of the cytoskeleton in heart failure
aKerckhoff Clinic, Department of Thoracic Surgery, Bad Nauheim, Germany
bDepartment of Experimental Cardiology, Max-Planck-Institute, Bad Nauheim, Germany
* Corresponding author jschaper{at}kerckhoff.mpg.de
The cytoskeleton of cardiac myocytes consists of actin, the intermediate filament desmin and of 
- and β-tubulin that form the microtubules by polymerization. Vinculin, talin, dystrophin and spectrin represent a separate group of membrane-associated proteins. In numerous experimental studies, the role of cytoskeletal alterations especially of microtubules and desmin, in cardiac hypertrophy and failure (CHF) has been described. Microtubules were found to be accumulated thereby posing an increased load on myocytes which impedes sarcomere motion and promotes cardiac dysfunction. Other groups were unable to confirm microtubular densification. The possibility exists that these changes are species, load and chamber dependent. Recently, damage of the dystrophin molecule and MLP (muscle LIM protein) were identified as possible causes of CHF. Our own studies in human hearts with chronic CHF due to dilated cardiomyopathy (DCM) showed that a morphological basis of reduced contractile function exists: the cytoskeletal and membrane-associated proteins are disorganized and increased in amount confirming experimental reports. In contrast, the contractile myofilaments and the proteins of the sarcomeric skeleton including titin, -actinin, and myomesin are significantly decreased. These changes can be assumed to occur in stages and are here presented as a testable hypothesis: (1) The early and reversible stage as present in animal experiments is characterized by accumulation of cytoskeletal proteins to counteract an increased strain without loss of contractile material. (2) Further accumulation of microtubules and desmin to compensate for the increasing loss of myofilaments and titin represents the late clinical and irreversible state. We suggest, based on a structural basis for heart failure, an integrative view which closes the gap between changes within cardiac myocytes and the involvement of the extracellular matrix, including the development of fibrosis. These factors contribute significantly to structural ventricular remodeling and dilatation finally resulting in reduced cardiac function.
KEYWORDS Cardiomyopathy; Heart failure; Contractile function; Remodeling; Ventricular function
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  R. Cortes, E. Rosello-Lleti, M. Rivera, L. Martinez-Dolz, A. Salvador, I. Azorin, and M. Portoles Influence of heart failure on nucleocytoplasmic transport in human cardiomyocytes Cardiovasc Res, November 6, 2009; (2009) cvp336v2. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Sartoretto, B. Y. Jin, M. Bauer, F. B. Gertler, R. Liao, and T. Michel Regulation of VASP phosphorylation in cardiac myocytes: differential regulation by cyclic nucleotides and modulation of protein expression in diabetic and hypertrophic heart Am J Physiol Heart Circ Physiol, November 1, 2009; 297(5): H1697 - H1710. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Cooper IV Proliferating cardiac microtubules Am J Physiol Heart Circ Physiol, August 1, 2009; 297(2): H510 - H511. [Full Text] [PDF]
|
|
|
|
|
|
M. Kuum, A. Kaasik, F. Joubert, R. Ventura-Clapier, and V. Veksler Energetic state is a strong regulator of sarcoplasmic reticulum Ca2+ loss in cardiac muscle: different efficiencies of different energy sources Cardiovasc Res, July 1, 2009; 83(1): 89 - 96. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Berni, M. Savi, L. Bocchi, F. Delucchi, E. Musso, C. Chaponnier, G. Gabbiani, S. Clement, and D. Stilli Modulation of actin isoform expression before the transition from experimental compensated pressure-overload cardiac hypertrophy to decompensation Am J Physiol Heart Circ Physiol, May 1, 2009; 296(5): H1625 - H1632. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Joubert, J. R. Wilding, D. Fortin, V. Domergue-Dupont, M. Novotova, R. Ventura-Clapier, and V. Veksler Local energetic regulation of sarcoplasmic and myosin ATPase is differently impaired in rats with heart failure J. Physiol., November 1, 2008; 586(21): 5181 - 5192. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Dhiman, E. S. Nakayasu, Y. H. Madaiah, B. K. Reynolds, J.-j. Wen, I. C. Almeida, and N. J. Garg Enhanced Nitrosative Stress during Trypanosoma cruzi Infection Causes Nitrotyrosine Modification of Host Proteins: Implications in Chagas' Disease Am. J. Pathol., September 1, 2008; 173(3): 728 - 740. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Lieber, H. Qiu, L. Chen, Y.-T. Shen, C. Hong, W. C. Hunter, N. Aubry, S. F. Vatner, and D. E. Vatner Cardiac dysfunction in aging conscious rats: altered cardiac cytoskeletal proteins as a potential mechanism Am J Physiol Heart Circ Physiol, August 1, 2008; 295(2): H860 - H866. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Cheng, M. R. Zile, M. Takahashi, C. F. Baicu, D. D. Bonnema, F. Cabral, D. R. Menick, and G. Cooper 4th A direct test of the hypothesis that increased microtubule network density contributes to contractile dysfunction of the hypertrophied heart Am J Physiol Heart Circ Physiol, May 1, 2008; 294(5): H2231 - H2241. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. A. Linke Sense and stretchability: The role of titin and titin-associated proteins in myocardial stress-sensing and mechanical dysfunction Cardiovasc Res, March 1, 2008; 77(4): 637 - 648. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Lin, G. P. Craig, L. Zhang, V. G. Yuen, M. Allard, J. H. McNeill, and K. M. MacLeod Acute inhibition of Rho-kinase improves cardiac contractile function in streptozotocin-diabetic rats Cardiovasc Res, July 1, 2007; 75(1): 51 - 58. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Yurukova, A. Kilic, K. Volker, K. Leineweber, N. Dybkova, L. S. Maier, O.-E. Brodde, and M. Kuhn CaMKII-mediated increased lusitropic responses to {beta}-adrenoreceptor stimulation in ANP-receptor deficient mice Cardiovasc Res, March 1, 2007; 73(4): 678 - 688. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Williams, A. L. Armesilla, T. M. A. Mohamed, C. L. Hagarty, F. H. McIntyre, S. Schomburg, A. O. Zaki, D. Oceandy, E. J. Cartwright, M. H. Buch, et al. The Sarcolemmal Calcium Pump, {alpha}-1 Syntrophin, and Neuronal Nitric-oxide Synthase Are Parts of a Macromolecular Protein Complex J. Biol. Chem., August 18, 2006; 281(33): 23341 - 23348. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Eiras, P. Fernandez, R. Pineiro, M. J. Iglesias, J. R. Gonzalez-Juanatey, and F. Lago Doxazosin induces activation of GADD153 and cleavage of focal adhesion kinase in cardiomyocytes en route to apoptosis Cardiovasc Res, July 1, 2006; 71(1): 118 - 128. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Nishimura, S. Nagai, M. Katoh, H. Yamashita, Y. Saeki, J.-i. Okada, T. Hisada, R. Nagai, and S. Sugiura Microtubules Modulate the Stiffness of Cardiomyocytes Against Shear Stress Circ. Res., January 6, 2006; 98(1): 81 - 87. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. J. Davis, J. B Pillai, M. Gupta, and M. P. Gupta Concurrent opposite effects of trichostatin A, an inhibitor of histone deacetylases, on expression of {alpha}-MHC and cardiac tubulins: implication for gain in cardiac muscle contractility Am J Physiol Heart Circ Physiol, March 1, 2005; 288(3): H1477 - H1490. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Schwartz, A. Duka, I. Duka, J. Cui, and H. Gavras Novel targets of ANG II regulation in mouse heart identified by serial analysis of gene expression Am J Physiol Heart Circ Physiol, November 1, 2004; 287(5): H1957 - H1966. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Makarenko, C.A. Opitz, M.C. Leake, C. Neagoe, M. Kulke, J.K. Gwathmey, F. del Monte, R.J. Hajjar, and W.A. Linke Passive Stiffness Changes Caused by Upregulation of Compliant Titin Isoforms in Human Dilated Cardiomyopathy Hearts Circ. Res., October 1, 2004; 95(7): 708 - 716. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Saffitz and A. G. Kleber Effects of Mechanical Forces and Mediators of Hypertrophy on Remodeling of Gap Junctions in the Heart Circ. Res., March 19, 2004; 94(5): 585 - 591. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Pan, T. Kislinger, A. O. Gramolini, E. Zvaritch, E. G. Kranias, D. H. MacLennan, and A. Emili Identification of biochemical adaptations in hyper- or hypocontractile hearts from phospholamban mutant mice by expression proteomics PNAS, February 24, 2004; 101(8): 2241 - 2246. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Ventura-Clapier, A. Garnier, and V. Veksler Energy metabolism in heart failure J. Physiol., February 15, 2004; 555(1): 1 - 13. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Tabibiazar, R. A. Wagner, A. Liao, and T. Quertermous Transcriptional Profiling of the Heart Reveals Chamber-Specific Gene Expression Patterns Circ. Res., December 12, 2003; 93(12): 1193 - 1201. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Miller, H. Musa, M. Gautel, and M. Peckham A targeted deletion of the C-terminal end of titin, including the titin kinase domain, impairs myofibrillogenesis J. Cell Sci., December 1, 2003; 116(23): 4811 - 4819. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Eigenthaler, S. Engelhardt, B. Schinke, A. Kobsar, E. Schmitteckert, S. Gambaryan, C. M. Engelhardt, V. Krenn, M. Eliava, T. Jarchau, et al. Disruption of cardiac Ena-VASP protein localization in intercalated disks causes dilated cardiomyopathy Am J Physiol Heart Circ Physiol, December 1, 2003; 285(6): H2471 - H2481. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Hunter, C. Neagoe, H. A. Jarvelainen, C. R. Martin, K. O. Lindros, W. A. Linke, and V. R. Preedy Alcohol Affects the Skeletal Muscle Proteins, Titin and Nebulin in Male and Female Rats J. Nutr., April 1, 2003; 133(4): 1154 - 1157. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Heineke, T. Kempf, T. Kraft, A. Hilfiker, H. Morawietz, R. J. Scheubel, P. Caroni, S. M. Lohmann, H. Drexler, and K. C. Wollert Downregulation of Cytoskeletal Muscle LIM Protein by Nitric Oxide: Impact on Cardiac Myocyte Hypertrophy Circulation, March 18, 2003; 107(10): 1424 - 1432. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Yun, M. J Zuscik, P. Gonzalez-Cabrera, D. F McCune, S. A Ross, R. Gaivin, M. T Piascik, and D. M Perez Gene expression profiling of {alpha}1b-adrenergic receptor-induced cardiac hypertrophy by oligonucleotide arrays Cardiovasc Res, February 1, 2003; 57(2): 443 - 455. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Steenman, Y.-W. Chen, M. Le Cunff, G. Lamirault, A. Varro, E. Hoffman, and J. J. Leger Transcriptomal analysis of failing and nonfailing human hearts Physiol Genomics, January 15, 2003; 12(2): 97 - 112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kupershmidt, I. C.-H. Yang, M. Sutherland, K.S. Wells, T. Yang, P. Yang, J. R. Balser, and D. M. Roden Cardiac-enriched LIM domain protein fhl2 is required to generate IKs in a heterologous system Cardiovasc Res, October 1, 2002; 56(1): 93 - 103. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. A. Poole-Wilson Death or repair of the myocyte in chronic heart failure J. Am. Coll. Cardiol., September 18, 2002; 40(6): 1104 - 1105. [Full Text] [PDF]
|
|
|
|
|
|
C. Neagoe, M. Kulke, F. del Monte, J. K. Gwathmey, P. P. de Tombe, R. J. Hajjar, and W. A. Linke Titin Isoform Switch in Ischemic Human Heart Disease Circulation, September 10, 2002; 106(11): 1333 - 1341. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. S. Harris, C. F. Baicu, C. H. Conrad, M. Koide, J. M. Buckley, M. Barnes, G. Cooper IV, and M. R. Zile Constitutive properties of hypertrophied myocardium: cellular contribution to changes in myocardial stiffness Am J Physiol Heart Circ Physiol, June 1, 2002; 282(6): H2173 - H2182. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Stroud, C. F. Baicu, M. A. Barnes, F. G. Spinale, and M. R. Zile Viscoelastic properties of pressure overload hypertrophied myocardium: effect of serine protease treatment Am J Physiol Heart Circ Physiol, June 1, 2002; 282(6): H2324 - H2335. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Communal, M. Sumandea, P. de Tombe, J. Narula, R. J. Solaro, and R. J. Hajjar Functional consequences of caspase activation in cardiac myocytes PNAS, April 30, 2002; 99(9): 6252 - 6256. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Kuhn, R Holtwick, H A Baba, J C Perriard, W Schmitz, and E Ehler Progressive cardiac hypertrophy and dysfunction in atrial natriuretic peptide receptor (GC-A) deficient mice Heart, April 1, 2002; 87(4): 368 - 374. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Motlagh, K. J Alden, B. Russell, and J. Garcia Sodium current modulation by a tubulin/GTP coupled process in rat neonatal cardiac myocytes J. Physiol., April 1, 2002; 540(1): 93 - 103. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J Balogh, M Merisckay, Z Li, D Paulin, and A Arner Hearts from mice lacking desmin have a myopathy with impaired active force generation and unaltered wall compliance Cardiovasc Res, February 1, 2002; 53(2): 439 - 450. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Razeghi, M. E. Young, J. L. Alcorn, C. S. Moravec, O.H. Frazier, and H. Taegtmeyer Metabolic Gene Expression in Fetal and Failing Human Heart Circulation, December 11, 2001; 104(24): 2923 - 2931. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Forini, A. Paolicchi, T. Pizzorusso, G. M. Ratto, M. Saviozzi, V. Vanini, and G. Iervasi 3,5,3'-Triiodothyronine deprivation affects phenotype and intracellular [Ca2+]i of human cardiomyocytes in culture Cardiovasc Res, August 1, 2001; 51(2): 322 - 330. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Babuty and M. J Lab Mechanoelectric contributions to sudden cardiac death Cardiovasc Res, May 1, 2001; 50(2): 270 - 279. [Full Text] [PDF]
|
|
|
|
|
|
H. Yoshida, K. Tanonaka, Y. Miyamoto, T. Abe, M. Takahashi, M. B Anand-Srivastava, and S. Takeo Characterization of cardiac myocyte and tissue {beta}-adrenergic signal transduction in rats with heart failure Cardiovasc Res, April 1, 2001; 50(1): 34 - 45. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Calaghan, J.-Y. Le Guennec, and E. White Modulation of Ca2+ Signaling by Microtubule Disruption in Rat Ventricular Myocytes and Its Dependence on the Ruptured Patch-Clamp Configuration Circ. Res., March 2, 2001; 88 (4): e32 - e37. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Keller, S.-Y. Shai, C. J. Babbitt, C. G. Pham, R. J. Solaro, M. L. Valencik, J. C. Loftus, and R. S. Ross Disruption of Integrin Function in the Murine Myocardium Leads to Perinatal Lethality, Fibrosis, and Abnormal Cardiac Performance Am. J. Pathol., March 1, 2001; 158(3): 1079 - 1090. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Communal, M. Sumandea, P. de Tombe, J. Narula, R. J. Solaro, and R. J. Hajjar Functional consequences of caspase activation in cardiac myocytes PNAS, April 30, 2002; 99(9): 6252 - 6256. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Omens, T. P. Usyk, Z. Li, and A. D. McCulloch Muscle LIM protein deficiency leads to alterations in passive ventricular mechanics Am J Physiol Heart Circ Physiol, February 1, 2002; 282(2): H680 - H687. [Abstract] [Full Text] [PDF]
|
|