| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2000 American Heart Association, Inc.
Clinical Research |
Myosin Heavy Chain Isoform Expression in the Failing and Nonfailing Human Heart
From the Department of Molecular, Cellular and Developmental Biology (S.M., L.A.L.), University of Colorado (Boulder); and Division of Cardiology (W.M., M.B.), University of Colorado Health Science Center (Denver).
Correspondence to Dr Leslie A. Leinwand, Department of Molecular, Cellular and Developmental Biology, University of Colorado at Boulder, Campus Box 347, Boulder, CO 80309-0347. E-mail Leslie.Leinwand{at}colorado.edu
Abstract—In the heart, the
relative proportions of the 2 forms of the motor protein myosin heavy
chain (MyHC) have been shown to be affected by a wide variety of
pathological and physiological stimuli. Hearts that
express the faster MyHC motor protein, 
, produce more power than
those expressing the slower MyHC motor protein, ß, leading to the
hypothesis that MyHC isoforms play a major role in the determination of
cardiac contractility. We showed previously that a
significant amount of MyHC mRNA is expressed in nonfailing human
ventricular myocardium and that MyHC mRNA
expression is decreased 15-fold in end-stage failing left ventricles.
In the present study, we determined the MyHC protein isoform
content of human heart samples of known MyHC mRNA composition. We
demonstrate that MyHC protein was easily detectable in 12 nonfailing
hearts. MyHC protein represented 7.2±3.2% of total
MyHC protein (compared with 
35% of the MyHC mRNA), suggesting that
translational regulation may be operative; in contrast, there was
effectively no detectable MyHC protein in the left ventricles of 10
end-stage failing human hearts.
Key Words: myosin • heart failure • isoforms
This article has been cited by other articles:
 |
|
 |
|
  J. A. Hill and E. N. Olson Cardiac Plasticity N. Engl. J. Med., March 27, 2008; 358(13): 1370 - 1380. [Full Text] [PDF]
|
|
|
|
 |
|
 J. B. Pillai, M. Chen, S. B. Rajamohan, S. Samant, V. B. Pillai, M. Gupta, and M. P. Gupta Activation of SIRT1, a class III histone deacetylase, contributes to fructose feeding-mediated induction of the {alpha}-myosin heavy chain expression Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1388 - H1397. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Hamdani, V. Kooij, S. van Dijk, D. Merkus, W. J. Paulus, C. d. Remedios, D. J. Duncker, G. J.M. Stienen, and J. van der Velden Sarcomeric dysfunction in heart failure Cardiovasc Res, March 1, 2008; 77(4): 649 - 658. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Hanft, F. S. Korte, and K. S. McDonald Cardiac function and modulation of sarcomeric function by length Cardiovasc Res, March 1, 2008; 77(4): 627 - 636. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Edwards Cardiac MHC gene expression: more complexity and a step forward Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H14 - H15. [Full Text] [PDF]
|
|
|
|
 |
|
 S. G. Haworth The cell and molecular biology of right ventricular dysfunction in pulmonary hypertension Eur. Heart J. Suppl., December 1, 2007; 9(suppl_H): H10 - H16. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Krenz, S. Sadayappan, H. E. Osinska, J. A. Henry, S. Beck, D. M. Warshaw, and J. Robbins Distribution and Structure-Function Relationship of Myosin Heavy Chain Isoforms in the Adult Mouse Heart J. Biol. Chem., August 17, 2007; 282(33): 24057 - 24064. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-K. Du, S. Morimoto, K. Nishii, R. Minakami, M. Ohta, N. Tadano, Q.-W. Lu, Y.-Y. Wang, D.-Y. Zhan, M. Mochizuki, et al. Knock-In Mouse Model of Dilated Cardiomyopathy Caused by Troponin Mutation Circ. Res., July 20, 2007; 101(2): 185 - 194. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. G. Daniels, T. Naya, V. L. M. Rundell, and P. P. de Tombe Development of contractile dysfunction in rat heart failure: hierarchy of cellular events Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2007; 293(1): R284 - R292. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. S. Korte and K. S. McDonald Sarcomere length dependence of rat skinned cardiac myocyte mechanical properties: dependence on myosin heavy chain J. Physiol., June 1, 2007; 581(2): 725 - 739. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. van Rooij, L. B. Sutherland, X. Qi, J. A. Richardson, J. Hill, and E. N. Olson Control of Stress-Dependent Cardiac Growth and Gene Expression by a MicroRNA Science, April 27, 2007; 316(5824): 575 - 579. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Herron, R. Vandenboom, E. Fomicheva, L. Mundada, T. Edwards, and J. M. Metzger Calcium-Independent Negative Inotropy by {beta}-Myosin Heavy Chain Gene Transfer in Cardiac Myocytes Circ. Res., April 27, 2007; 100(8): 1182 - 1190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Stelzer, S. L. Brickson, M. R. Locher, and R. L. Moss Role of myosin heavy chain composition in the stretch activation response of rat myocardium J. Physiol., February 15, 2007; 579(1): 161 - 173. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Schoffstall, N. M. Brunet, S. Williams, V. F. Miller, A. T. Barnes, F. Wang, L. A. Compton, L. A. McFadden, D. W. Taylor, M. Seavy, et al. Ca2+ sensitivity of regulated cardiac thin filament sliding does not depend on myosin isoform J. Physiol., December 15, 2006; 577(3): 935 - 944. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Tschirgi, I. Rajapakse, and M. Chandra Functional consequence of mutation in rat cardiac troponin T is affected differently by myosin heavy chain isoforms J. Physiol., July 1, 2006; 574(1): 263 - 273. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Kong, P. Tannous, G. Lu, K. Berenji, B. A. Rothermel, E. N. Olson, and J. A. Hill Suppression of Class I and II Histone Deacetylases Blunts Pressure-Overload Cardiac Hypertrophy Circulation, June 6, 2006; 113(22): 2579 - 2588. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Xing, T.-C. Zhang, D. Cao, Z. Wang, C. L. Antos, S. Li, Y. Wang, E. N. Olson, and D.-Z. Wang Myocardin Induces Cardiomyocyte Hypertrophy Circ. Res., April 28, 2006; 98(8): 1089 - 1097. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Perrino and H. A. Rockman GATA4 and the Two Sides of Gene Expression Reprogramming Circ. Res., March 31, 2006; 98(6): 715 - 716. [Full Text] [PDF]
|
|
|
|
 |
|
 K. W. Chaudhary, N. X. Barrezueta, M. B. Bauchmann, A. J. Milici, G. Beckius, D. B. Stedman, J. E. Hambor, W. L. Blake, J. D. McNeish, A. Bahinski, et al. Embryonic Stem Cells in Predictive Cardiotoxicity: Laser Capture Microscopy Enables Assay Development Toxicol. Sci., March 1, 2006; 90(1): 149 - 158. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kenessey, E. A. Sullivan, and K. Ojamaa Nuclear localization of protein kinase C-{alpha} induces thyroid hormone receptor-{alpha}1 expression in the cardiomyocyte Am J Physiol Heart Circ Physiol, January 1, 2006; 290(1): H381 - H389. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Emter, S. A. McCune, G. C. Sparagna, M. J. Radin, and R. L. Moore Low-intensity exercise training delays onset of decompensated heart failure in spontaneously hypertensive heart failure rats Am J Physiol Heart Circ Physiol, November 1, 2005; 289(5): H2030 - H2038. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Kuzman, T. A. Thomas, K. A. Vogelsang, S. Said, B. E. Anderson, and A. M. Gerdes Effects of induced hyperthyroidism in normal and cardiomyopathic hamsters J Appl Physiol, October 1, 2005; 99(4): 1428 - 1433. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. S. Korte, T. J. Herron, M. J. Rovetto, and K. S. McDonald Power output is linearly related to MyHC content in rat skinned myocytes and isolated working hearts Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H801 - H812. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Carniel, M. R.G. Taylor, G. Sinagra, A. Di Lenarda, L. Ku, P. R. Fain, M. M. Boucek, J. Cavanaugh, S. Miocic, D. Slavov, et al. {alpha}-Myosin Heavy Chain: A Sarcomeric Gene Associated With Dilated and Hypertrophic Phenotypes of Cardiomyopathy Circulation, July 5, 2005; 112(1): 54 - 59. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Fraccarollo, P. Galuppo, I. Schmidt, G. Ertl, and J. Bauersachs Additive amelioration of left ventricular remodeling and molecular alterations by combined aldosterone and angiotensin receptor blockade after myocardial infarction Cardiovasc Res, July 1, 2005; 67(1): 97 - 105. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-M. Gao, H. Kiriazis, X.-L. Moore, X.-H. Feng, K. Sheppard, A. Dart, and X.-J. Du Regression of pressure overload-induced left ventricular hypertrophy in mice Am J Physiol Heart Circ Physiol, June 1, 2005; 288(6): H2702 - H2707. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Vellaichamy, M. L. Khurana, J. Fink, and K. N. Pandey Involvement of the NF-{kappa}B/Matrix Metalloproteinase Pathway in Cardiac Fibrosis of Mice Lacking Guanylyl Cyclase/Natriuretic Peptide Receptor A J. Biol. Chem., May 13, 2005; 280(19): 19230 - 19242. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.J. Marian On Mice, Rabbits, and Human Heart Failure Circulation, May 10, 2005; 111(18): 2276 - 2279. [Full Text] [PDF]
|
|
|
|
|
|
J. James, L. Martin, M. Krenz, C. Quatman, F. Jones, R. Klevitsky, J. Gulick, and J. Robbins Forced Expression of {alpha}-Myosin Heavy Chain in the Rabbit Ventricle Results in Cardioprotection Under Cardiomyopathic Conditions Circulation, May 10, 2005; 111(18): 2339 - 2346. [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]
|
|
|
|
|
|
V. L. M. Rundell, V. Manaves, A. F. Martin, and P. P. de Tombe Impact of {beta}-myosin heavy chain isoform expression on cross-bridge cycling kinetics Am J Physiol Heart Circ Physiol, February 1, 2005; 288(2): H896 - H903. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N.A. Narolska, R.B. van Loon, N.M. Boontje, R. Zaremba, S. E. Penas, J. Russell, S.R. Spiegelenberg, M.A.J.M. Huybregts, F.C. Visser, J.W. de Jong, et al. Myocardial contraction is 5-fold more economical in ventricular than in atrial human tissue Cardiovasc Res, January 1, 2005; 65(1): 221 - 229. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Krenz and J. Robbins Impact of beta-myosin heavy chain expression on cardiac function during stress J. Am. Coll. Cardiol., December 21, 2004; 44(12): 2390 - 2397. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. SHARMA, J. V. ADROGUE, L. GOLFMAN, I. URAY, J. LEMM, K. YOUKER, G. P. NOON, O. H FRAZIER, and H. TAEGTMEYER Intramyocardial lipid accumulation in the failing human heart resembles the lipotoxic rat heart FASEB J, November 1, 2004; 18(14): 1692 - 1700. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. C. Sucharov, S. M. Helmke, S. J. Langer, M. B. Perryman, M. Bristow, and L. Leinwand The Ku Protein Complex Interacts with YY1, Is Up-Regulated in Human Heart Failure, and Represses {alpha} Myosin Heavy-Chain Gene Expression Mol. Cell. Biol., October 1, 2004; 24(19): 8705 - 8715. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. P.M van Empel and L. J De Windt Myocyte hypertrophy and apoptosis: a balancing act Cardiovasc Res, August 15, 2004; 63(3): 487 - 499. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Bupha-Intr and J. Wattanapermpool Cardioprotective effects of exercise training on myofilament calcium activation in ovariectomized rats J Appl Physiol, May 1, 2004; 96(5): 1755 - 1760. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Huang, K.E. Walker, F. Hanley, J. Narula, S.R. Houser, and T.N. Tulenko Cardiac Systolic and Diastolic Dysfunction After a Cholesterol-Rich Diet Circulation, January 6, 2004; 109(1): 97 - 102. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Yamashita, S. Sugiura, H. Fujita, S.-i. Yasuda, R. Nagai, Y. Saeki, K. Sunagawa, and H. Sugi Myosin light chain isoforms modify force-generating ability of cardiac myosin by changing the kinetics of actin-myosin interaction Cardiovasc Res, December 1, 2003; 60(3): 580 - 588. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. N. Sabbah, V. G. Sharov, R. C. Gupta, S. Mishra, S. Rastogi, A. I. Undrovinas, P. A. Chaudhry, A. Todor, T. Mishima, E. J. Tanhehco, et al. Reversal of Chronic Molecular and Cellular Abnormalities Due to Heart Failure by Passive Mechanical Ventricular Containment Circ. Res., November 28, 2003; 93(11): 1095 - 1101. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Gupta, V. Sueblinvong, J. Raman, V. Jeevanandam, and M. P. Gupta Single-stranded DNA-binding Proteins PUR{alpha} and PUR{beta} Bind to a Purine-rich Negative Regulatory Element of the {alpha}-Myosin Heavy Chain Gene and Control Transcriptional and Translational Regulation of the Gene Expression: IMPLICATIONS IN THE REPRESSION OF {alpha}-MYOSIN HEAVY CHAIN DURING HEART FAILURE J. Biol. Chem., November 7, 2003; 278(45): 44935 - 44948. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Haddad, P. W. Bodell, A. X. Qin, J. M. Giger, and K. M. Baldwin Role of Antisense RNA in Coordinating Cardiac Myosin Heavy Chain Gene Switching J. Biol. Chem., September 26, 2003; 278(39): 37132 - 37138. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X.-M. Gao, A. Agrotis, D. J. Autelitano, E. Percy, E. A. Woodcock, G. L. Jennings, A. M. Dart, and X.-J. Du Sex Hormones and Cardiomyopathic Phenotype Induced by Cardiac {beta}2-Adrenergic Receptor Overexpression Endocrinology, September 1, 2003; 144(9): 4097 - 4105. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. N. Olson and M. D. Schneider Sizing up the heart: development redux in disease Genes & Dev., August 15, 2003; 17(16): 1937 - 1956. [Full Text] [PDF]
|
|
|
|
|
|
L. W. Stevenson Clinical Use of Inotropic Therapy for Heart Failure: Looking Backward or Forward?: Part II: Chronic Inotropic Therapy Circulation, July 29, 2003; 108(4): 492 - 497. [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Henning and Y. Li Cocaine Produces Cardiac Hypertrophy by Protein Kinase C Dependent Mechanisms Journal of Cardiovascular Pharmacology and Therapeutics, June 1, 2003; 8(2): 149 - 160. [Abstract] [PDF]
|
|
|
|
|
|
W. H. Barry and E. M. Gilbert How Do {beta}-Blockers Improve Ventricular Function in Patients With Congestive Heart Failure? Circulation, May 20, 2003; 107(19): 2395 - 2397. [Full Text] [PDF]
|
|
|
|
|
|
M. Krenz, A. Sanbe, F. Bouyer-Dalloz, J. Gulick, R. Klevitsky, T. E. Hewett, H. E. Osinska, J. N. Lorenz, C. Brosseau, A. Federico, et al. Analysis of Myosin Heavy Chain Functionality in the Heart J. Biol. Chem., May 2, 2003; 278(19): 17466 - 17474. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. Houser and K. B. Margulies Is Depressed Myocyte Contractility Centrally Involved in Heart Failure? Circ. Res., March 7, 2003; 92(4): 350 - 358. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J van der Velden, Z Papp, R Zaremba, N.M Boontje, J.W de Jong, V.J Owen, P.B.J Burton, P Goldmann, K Jaquet, and G.J.M Stienen Increased Ca2+-sensitivity of the contractile apparatus in end-stage human heart failure results from altered phosphorylation of contractile proteins Cardiovasc Res, January 1, 2003; 57(1): 37 - 47. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. S. McDonald and T. J. Herron It Takes "Heart" to Win: What Makes the Heart Powerful? Physiology, October 1, 2002; 17(5): 185 - 190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Herron and K. S. McDonald Small Amounts of {alpha}-Myosin Heavy Chain Isoform Expression Significantly Increase Power Output of Rat Cardiac Myocyte Fragments Circ. Res., June 14, 2002; 90(11): 1150 - 1152. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. L.J.L Thijssen, H. M.W van der Velden, E. P van Ankeren, J. Ausma, M. A Allessie, M. Borgers, G. J.J.M van Eys, and H. J Jongsma Analysis of altered gene expression during sustained atrial fibrillation in the goat Cardiovasc Res, May 1, 2002; 54(2): 427 - 437. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Fraccarollo, J. Bauersachs, M. Kellner, P. Galuppo, and G. Ertl Cardioprotection by long-term ETA receptor blockade and ACE inhibition in rats with congestive heart failure: mono- versus combination therapy Cardiovasc Res, April 1, 2002; 54(1): 85 - 94. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Herron, F. S. Korte, and K. S. McDonald Loaded shortening and power output in cardiac myocytes are dependent on myosin heavy chain isoform expression Am J Physiol Heart Circ Physiol, September 1, 2001; 281(3): H1217 - H1222. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J. ARONOW, T. TOYOKAWA, A. CANNING, K. HAGHIGHI, U. DELLING, E. KRANIAS, J. D. MOLKENTIN, and G. W. DORN II Divergent transcriptional responses to independent genetic causes of cardiac hypertrophy Physiol Genomics, June 6, 2001; 6(1): 19 - 28. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|