© 1997 American Heart Association, Inc.
Articles |
Cytoskeletal Mechanics in Pressure-Overload Cardiac Hypertrophy
the Cardiology Section of the Department of Medicine and the Department of Physiology, Gazes Cardiac Research Institute, Medical University of South Carolina, and the Veterans Administration Medical Center (H.T., T.N., M.R.Z, G.C. IV), Charleston, SC; the Physiology Program (N.W.), Harvard School of Public Health, Boston, Mass; and the Departments of Surgery and Pathology (D.E.I.), Children's Hospital and Harvard Medical School, Boston, Mass.
We have shown that the cellular contractile dysfunction characteristic of pressure-overload cardiac hypertrophy results not from an abnormality intrinsic to the myofilament portion of the cardiocyte cytoskeleton but rather from an increased density of the microtubule component of the extramyofilament portion of the cardiocyte cytoskeleton. To determine how, in physical terms, this increased microtubule density mechanically overloads the contractile apparatus at the cellular level, we measured cytoskeletal stiffness and apparent viscosity in isolated cardiocytes via magnetic twisting cytometry, a technique by which magnetically induced force is applied directly to the cytoskeleton through integrin-coupled ferromagnetic beads coated with Arg-Gly-Asp (RGD) peptide. Measurements were made in two groups of cardiocytes from cats with right ventricular (RV) hypertrophy induced by pulmonary artery banding: (1) those from the pressure-overloaded RV and (2) those from the normally loaded same-animal control left ventricle (LV). Cytoskeletal stiffness increased almost twofold, from 8.53±0.77 dyne/cm2 in the normally loaded LV cardiocytes to 16.46±1.32 dyne/cm2 in the hypertrophied RV cardiocytes. Cytoskeletal apparent viscosity increased almost fourfold, from 20.97±1.92 poise in the normally loaded LV cardiocytes to 87.85±6.95 poise in the hypertrophied RV cardiocytes. In addition to these baseline data showing differing stiffness and, especially, apparent viscosity in the two groups of cardiocytes, microtubule depolymerization by colchicine was found to return both the stiffness and the apparent viscosity of the pressure overload–hypertrophied RV cells fully to normal. Conversely, microtubule hyperpolymerization by taxol increased the stiffness and apparent viscosity values of normally loaded LV cardiocytes to the abnormal values given above for pressure-hypertrophied RV cardiocytes. Thus, increased microtubule density constitutes primarily a viscous load on the cardiocyte contractile apparatus in pressure-overload cardiac hypertrophy.
Key Words: hypertrophy • cardiocyte • cytoskeleton • microtubule
This article has been cited by other articles:
 |
|
 |
|
  J. T. Fassett, X. Xu, X. Hu, G. Zhu, J. French, Y. Chen, and R. J. Bache Adenosine regulation of microtubule dynamics in cardiac hypertrophy Am J Physiol Heart Circ Physiol, August 1, 2009; 297(2): H523 - H532. [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]
|
|
|
|
 |
|
 J. Davis, M. V. Westfall, D. Townsend, M. Blankinship, T. J. Herron, G. Guerrero-Serna, W. Wang, E. Devaney, and J. M. Metzger Designing Heart Performance by Gene Transfer Physiol Rev, October 1, 2008; 88(4): 1567 - 1651. [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]
|
|
|
|
 |
|
 J. Sui, J. Zhang, T. L. Tan, C. B. Ching, and W. N. Chen Comparative Proteomics Analysis of Vascular Smooth Muscle Cells Incubated with S- and R-Enantiomers of Atenolol Using iTRAQ-coupled Two-dimensional LC-MS/MS Mol. Cell. Proteomics, June 1, 2008; 7(6): 1007 - 1018. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. Sackett, L. Ozbun, E. Zudaire, L. Wessner, J. M. Chirgwin, F. Cuttitta, and A. Martinez Intracellular Proadrenomedullin-Derived Peptides Decorate the Microtubules and Contribute to Cytoskeleton Function Endocrinology, June 1, 2008; 149(6): 2888 - 2898. [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]
|
|
|
|
 |
|
 P. Pokreisz, G. Marsboom, and S. Janssens Pressure overload-induced right ventricular dysfunction and remodelling in experimental pulmonary hypertension: the right heart revisited Eur. Heart J. Suppl., December 1, 2007; 9(suppl_H): H75 - H84. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. K Parker and D. E Ingber Extracellular matrix, mechanotransduction and structural hierarchies in heart tissue engineering Phil Trans R Soc B, August 29, 2007; 362(1484): 1267 - 1279. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M. R. Carvalho, R. A. Bassani, K. G. Franchini, and J. W. M. Bassani Enhanced calcium mobilization in rat ventricular myocytes during the onset of pressure overload-induced hypertrophy Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1803 - H1813. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Cooper IV Cytoskeletal networks and the regulation of cardiac contractility: microtubules, hypertrophy, and cardiac dysfunction Am J Physiol Heart Circ Physiol, September 1, 2006; 291(3): H1003 - H1014. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Scholz, P. McDermott, M. Garnovskaya, T. N. Gallien, S. Huettelmaier, C. DeRienzo, and G. Cooper IV Microtubule-associated protein-4 (MAP-4) inhibits microtubule-dependent distribution of mRNA in isolated neonatal cardiocytes Cardiovasc Res, August 1, 2006; 71(3): 506 - 516. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. P. Brangwynne, F. C. MacKintosh, S. Kumar, N. A. Geisse, J. Talbot, L. Mahadevan, K. K. Parker, D. E. Ingber, and D. A. Weitz Microtubules can bear enhanced compressive loads in living cells because of lateral reinforcement J. Cell Biol., June 5, 2006; 173(5): 733 - 741. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D. McCulloch and J. H. Omens Myocyte Shearing, Myocardial Sheets, and Microtubules Circ. Res., January 6, 2006; 98(1): 1 - 3. [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]
|
|
|
|
|
|
N. Buscemi, C. Murray, A. Doherty-Kirby, G. Lajoie, M. A. Sussman, and J. E. Van Eyk Myocardial subproteomic analysis of a constitutively active Rac1-expressing transgenic mouse with lethal myocardial hypertrophy Am J Physiol Heart Circ Physiol, December 1, 2005; 289(6): H2325 - H2333. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Cheng, F. Qiao, T. N. Gallien, D. Kuppuswamy, and G. Cooper IV Inhibition of {beta}-adrenergic receptor trafficking in adult cardiocytes by MAP4 decoration of microtubules Am J Physiol Heart Circ Physiol, March 1, 2005; 288(3): H1193 - H1202. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Takahashi, H. Shiraishi, Y. Ishibashi, K. L. Blade, P. J. McDermott, D. R. Menick, D. Kuppuswamy, and G. Cooper IV Phenotypic consequences of {beta}1-tubulin expression and MAP4 decoration of microtubules in adult cardiocytes Am J Physiol Heart Circ Physiol, November 1, 2003; 285(5): H2072 - H2083. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ishibashi, M. Takahashi, Y. Isomatsu, F. Qiao, Y. Iijima, H. Shiraishi, J. M. Simsic, C. F. Baicu, J. Robbins, M. R. Zile, et al. Role of microtubules versus myosin heavy chain isoforms in contractile dysfunction of hypertrophied murine cardiocytes Am J Physiol Heart Circ Physiol, August 7, 2003; 285(3): H1270 - H1285. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. E. Ingber Tensegrity II. How structural networks influence cellular information processing networks J. Cell Sci., April 15, 2003; 116(8): 1397 - 1408. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. E. Ingber Tensegrity I. Cell structure and hierarchical systems biology J. Cell Sci., April 1, 2003; 116(7): 1157 - 1173. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. G. Dos Remedios, D. Chhabra, M. Kekic, I. V. Dedova, M. Tsubakihara, D. A. Berry, and N. J. Nosworthy Actin Binding Proteins: Regulation of Cytoskeletal Microfilaments Physiol Rev, April 1, 2003; 83(2): 433 - 473. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. S. Scopacasa, V. P. A. Teixeira, and K. G. Franchini Colchicine attenuates left ventricular hypertrophy but preserves cardiac function of aortic-constricted rats J Appl Physiol, April 1, 2003; 94(4): 1627 - 1633. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. E. Ingber Mechanical Signaling and the Cellular Response to Extracellular Matrix in Angiogenesis and Cardiovascular Physiology Circ. Res., November 15, 2002; 91(10): 877 - 887. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Collinsworth, S. Zhang, W. E. Kraus, and G. A. Truskey Apparent elastic modulus and hysteresis of skeletal muscle cells throughout differentiation Am J Physiol Cell Physiol, October 1, 2002; 283(4): C1219 - C1227. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Schroder, K. Tobita, J. P. Tinney, J. K. Foldes, and B. B. Keller Microtubule Involvement in the Adaptation to Altered Mechanical Load in Developing Chick Myocardium Circ. Res., August 23, 2002; 91(4): 353 - 359. [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]
|
|
|
|
 |
|
 X. Yang, P. J I Salas, T. V Pham, B. J Wasserlauf, M. J D Smets, R. J Myerburg, H. Gelband, B. F Hoffman, and A. L Bassett Cytoskeletal actin microfilaments and the transient outward potassium current in hypertrophied rat ventriculocytes J. Physiol., June 1, 2002; 541(2): 411 - 421. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Zile and D. L. Brutsaert New Concepts in Diastolic Dysfunction and Diastolic Heart Failure: Part II: Causal Mechanisms and Treatment Circulation, March 26, 2002; 105(12): 1503 - 1508. [Full Text] [PDF]
|
|
|
|
|
|
M. Puig-De-Morales, M. Grabulosa, J. Alcaraz, J. Mullol, G. N. Maksym, J. J. Fredberg, and D. Navajas Measurement of cell microrheology by magnetic twisting cytometry with frequency domain demodulation J Appl Physiol, September 1, 2001; 91(3): 1152 - 1159. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Chen, B. Fabry, E. L. Schiffrin, and N. Wang Twisting integrin receptors increases endothelin-1 gene expression in endothelial cells Am J Physiol Cell Physiol, June 1, 2001; 280(6): C1475 - C1484. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. G. Kerfant, G. Vassort, and A. M. Gomez Microtubule Disruption by Colchicine Reversibly Enhances Calcium Signaling in Intact Rat Cardiac Myocytes Circ. Res., April 13, 2001; 88 (7): e59 - e65. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Zile, G. R. Green, G. T. Schuyler, G. P. Aurigemma, D. C. Miller, and G. Cooper IV Cardiocyte cytoskeleton in patients with left ventricular pressure overload hypertrophy J. Am. Coll. Cardiol., March 15, 2001; 37(4): 1080 - 1084. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A Kamkin, I Kiseleva, and G Isenberg Stretch-activated currents in ventricular myocytes: amplitude and arrhythmogenic effects increase with hypertrophy Cardiovasc Res, December 1, 2000; 48(3): 409 - 420. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Koide, M. Hamawaki, T. Narishige, H. Sato, S. Nemoto, G. DeFreyte, M. R. Zile, G. Cooper IV, and B. A. Carabello Microtubule Depolymerization Normalizes In Vivo Myocardial Contractile Function in Dogs With Pressure-Overload Left Ventricular Hypertrophy Circulation, August 29, 2000; 102(9): 1045 - 1052. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. J. Heller, D. E. Mohrman, and J. R. Prohaska Decreased passive stiffness of cardiac myocytes and cardiac tissue from copper-deficient rat hearts Am J Physiol Heart Circ Physiol, June 1, 2000; 278(6): H1840 - H1847. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Webster and D. L. Patrick Beating rate of isolated neonatal cardiomyocytes is regulated by the stable microtubule subset Am J Physiol Heart Circ Physiol, May 1, 2000; 278(5): H1653 - H1661. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Heling, R. Zimmermann, S. Kostin, Y. Maeno, S. Hein, B. Devaux, E. Bauer, W.-P. Klovekorn, M. Schlepper, W. Schaper, et al. Increased Expression of Cytoskeletal, Linkage, and Extracellular Proteins in Failing Human Myocardium Circ. Res., April 28, 2000; 86(8): 846 - 853. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Walker, F. A. Crawford Jr, and F. G. Spinale MYOCYTE CONTRACTILE DYSFUNCTION WITH HYPERTROPHY AND FAILURE: RELEVANCE TO CARDIAC SURGERY J. Thorac. Cardiovasc. Surg., February 1, 2000; 119(2): 388 - 400. [Full Text] [PDF]
|
|
|
|
|
|
S. Hein, S. Kostin, A. Heling, Y. Maeno, and J. Schaper The role of the cytoskeleton in heart failure Cardiovasc Res, January 14, 2000; 45(2): 273 - 278. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Gomez, B. G. Kerfant, and G. Vassort Microtubule Disruption Modulates Ca2+ Signaling in Rat Cardiac Myocytes Circ. Res., January 7, 2000; 86(1): 30 - 36. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Samain, H. Bouillier, C. Perret, M. Safar, and G. Dagher ANG II-induced Ca2+ increase in smooth muscle cells from SHR is regulated by actin and microtubule networks Am J Physiol Heart Circ Physiol, August 1, 1999; 277(2): H834 - H841. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. INGBER How cells (might) sense microgravity FASEB J, May 1, 1999; 13(9001): 3 - 15. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F C Howarth, S C Calaghan, M R Boyett, and E White Effect of the microtubule polymerizing agent taxol on contraction, Ca2+ transient and L-type Ca2+ current in rat ventricular myocytes J. Physiol., April 15, 1999; 516(2): 409 - 419. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Narishige, K. L. Blade, Y. Ishibashi, T. Nagai, M. Hamawaki, D. R. Menick, D. Kuppuswamy, and G. Cooper IV Cardiac Hypertrophic and Developmental Regulation of the beta -Tubulin Multigene Family J. Biol. Chem., April 2, 1999; 274(14): 9692 - 9697. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Zile, M. Koide, H. Sato, Y. Ishiguro, C. H. Conrad, J. M. Buckley, J. P. Morgan, and G. Cooper IV Role of microtubules in the contractile dysfunction of hypertrophied myocardium J. Am. Coll. Cardiol., January 1, 1999; 33(1): 250 - 260. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Cicogna, K. G. Robinson, C. H. Conrad, K. Singh, R. Squire, M. P. Okoshi, and O. H. L. Bing Direct Effects of Colchicine on Myocardial Function : Studies in Hypertrophied and Failing Spontaneously Hypertensive Rats Hypertension, January 1, 1999; 33(1): 60 - 65. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M. Palmer, S. Valent, E. L. Holder, H. D. Weinberger, and R. D. Bies Microtubules modulate cardiomyocyte beta -adrenergic response in cardiac hypertrophy Am J Physiol Heart Circ Physiol, November 1, 1998; 275(5): H1707 - H1716. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. B. New, J. L. Zellner, L. Hebbar, R. Mukherjee, A. C. Sampson, J. W. Hendrick, J. R. Handy, F. Crawford Jr., and F. G. Spinale Isolated left ventricular myocyte contractility in patients undergoing cardiac operations J. Thorac. Cardiovasc. Surg., September 1, 1998; 116(3): 495 - 499. [Abstract] [Full Text]
|
|
|
|
|
|
M. R. Zile, K. Richardson, M. K. Cowles, J. M. Buckley, M. Koide, B. A. Cowles, V. Gharpuray, and G. Cooper IV Constitutive Properties of Adult Mammalian Cardiac Muscle Cells Circulation, August 11, 1998; 98(6): 567 - 579. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Wang Mechanical Interactions Among Cytoskeletal Filaments Hypertension, July 1, 1998; 32(1): 162 - 165. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. U Sys, G. W De Keulenaer, and D. L Brutsaert Physiopharmacological evaluation of myocardial performance: how to study modulation by cardiac endothelium and related humoral factors? Cardiovasc Res, July 1, 1998; 39(1): 136 - 147. [Full Text] [PDF]
|
|
|
|
|
|
A. M Shah, S. J Sollott, and E. G Lakatta Physio-pharmacological evaluation of myocardial performance: an integrative approach Cardiovasc Res, July 1, 1998; 39(1): 148 - 154. [Full Text] [PDF]
|
|
|
|
|
|
M. R. Zile, M. K. Cowles, J. M. Buckley, K. Richardson, B. A. Cowles, C. F. Baicu, G. Cooper IV, and V. Gharpuray Gel stretch method: a new method to measure constitutive properties of cardiac muscle cells Am J Physiol Heart Circ Physiol, June 1, 1998; 274(6): H2188 - H2202. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Tagawa, M. Koide, H. Sato, M. R. Zile, B. A. Carabello, and G. Cooper IV Cytoskeletal Role in the Transition From Compensated to Decompensated Hypertrophy During Adult Canine Left Ventricular Pressure Overloading Circ. Res., April 20, 1998; 82(7): 751 - 761. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. E. D. J. ter Keurs Microtubules in Cardiac Hypertrophy : A Mechanical Role in Decompensation? Circ. Res., April 20, 1998; 82(7): 828 - 831. [Full Text] [PDF]
|
|
|
|
|
|
P. P de Tombe Altered contractile function in heart failure Cardiovasc Res, February 1, 1998; 37(2): 367 - 380. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Putnam, J. Cunningham, R. Dennis, J. Linderman, and D. Mooney Microtubule assembly is regulated by externally applied strain in cultured smooth muscle cells J. Cell Sci., January 11, 1998; 111(22): 3379 - 3387. [Abstract] [PDF]
|
|
|
|
|
|
T. J. Fraites Jr, A. Saeki, and D. A. Kass Effect of Altering Filling Pattern on Diastolic Pressure-Volume Curve Circulation, December 16, 1997; 96(12): 4408 - 4414. [Abstract] [Full Text]
|
|
|
|
|
|
H. Sato, T. Nagai, D. Kuppuswamy, T. Narishige, M. Koide, D. R. Menick, and G. Cooper IV Microtubule Stabilization in Pressure Overload Cardiac Hypertrophy J. Cell Biol., November 17, 1997; 139(4): 963 - 973. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kulke, S. Fujita-Becker, E. Rostkova, C. Neagoe, D. Labeit, D. J. Manstein, M. Gautel, and W. A. Linke Interaction Between PEVK-Titin and Actin Filaments: Origin of a Viscous Force Component in Cardiac Myofibrils Circ. Res., November 9, 2001; 89(10): 874 - 881. [Abstract] [Full Text] [PDF]
|
|