Multi-scale computational models of familial hypertrophic cardiomyopathy: Genotype to phenotype

Journal of the Royal Society Interface

Volumn 8, Issue 64, 2011, Pages 1550-1561

  Campbell, Stuart G ^a,b   McCulloch, Andrew D ^a  

^a UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

^b UNIVERSITY OF KENTUCKY   (United States)

Author keywords

Cardiac muscle; Hypertrophic cardiomyopathy; Multi scale

Indexed keywords

ANIMALS; GENES; HEART; MUSCLE; PATIENT TREATMENT;

BIOPHYSICAL DATA; CARDIAC CELL; CARDIAC DEATH; CARDIAC MUSCLES; CLINICAL MANAGEMENT; COMPUTATIONAL ANALYSIS; COMPUTATIONAL MODEL; CONTRACTILE DYSFUNCTION; DYNAMIC PROCESS; FAMILIAL HYPERTROPHIC CARDIOMYOPATHIES; GENES ENCODING; GENETICALLY MODIFIED; HEART FAILURE; HEART FUNCTION; HYPERTROPHIC CARDIOMYOPATHY; INHERITED DISORDERS; MULTISCALE MODELS; MULTISCALES; MUTANT PROTEINS; MYOCARDIAL STRAIN; MYOCARDIAL TISSUE; PATIENT POPULATION; PUMP FUNCTION; RISK STRATIFICATION; SARCOMERIC PROTEIN; SUDDEN DEATHS; VENTRICULAR WALLS;

COMPUTER SIMULATION;

ACTIN; ALPHA TROPOMYOSIN; CALCIUM ION; MYOSIN HEAVY CHAIN BETA; TROPOMYOSIN; TROPONIN C; TROPONIN I; TROPONIN T;

FAMILIAL HYPERTROPHIC CARDIOMYOPATHY; GENE MUTATION; GENETIC HETEROGENEITY; GENETIC LINKAGE; GENOTYPE; HEART FUNCTION; HIDDEN MARKOV MODEL; HUMAN; IN VITRO STUDY; IN VIVO STUDY; MATHEMATICAL MODEL; MOLECULAR DYNAMICS; MULTISCALE COMPUTATIONAL MODEL; MYOFILAMENT; NONHUMAN; PHENOTYPE; REVIEW;

ANIMALIA;

EID: 80054770583     PISSN: 17425689     EISSN: 17425662     Source Type: Journal    
DOI: 10.1098/rsif.2011.0184     Document Type: Review

References (78)

1. Trayanova, N. A. 2011 Whole-heart modeling: applications to cardiac electrophysiology and electromechanics. Circ. Res. 108, 113-128. (doi:10.1161/CIRCRESAHA.110.223610)
2. Maron, B. J., Gardin, J. M., Flack, J. M., Gidding, S. S., Kurosaki, T. T. & Bild, D. E. 1995 Prevalence of hypertrophic cardiomyopathy in a general population of young adults. Echocardiographic analysis of 4111 subjects in the CARDIA Study. Coronary Artery Risk Development in (Young) Adults. Circulation 92, 785-789.
3. Force, T. et al. 2010 Research priorities in hypertrophic cardiomyopathy: report of a Working Group of the National Heart, Lung and Blood Institute. Circulation 122, 1130-1133. (doi:10.1161/CIRCULATIONAHA.110.950089)
4. Coats, C. J. & Elliott, P. M. 2008 Current management of hypertrophic cardiomyopathy. Curr. Treat Options Cardiovasc. Med. 10, 496-504. (doi:10.1007/s11936-008-0042-9)
5. Geisterfer-Lowrance, A. A., Kass, S., Tanigawa, G., Vosberg, H. P., Mckenna, W., Seidman, C. E. & Seidman, J. G. 1990 A molecular basis for familial hypertrophic cardiomyopathy: a beta cardiac myosin heavy chain gene missense mutation. Cell 62, 999-1006. (doi:10.1016/0092-8674(90)90274-I)
6. Seidman, C. E. & Seidman, J. G. 2011 Identifying sarcomere gene mutations in hypertrophic cardiomyopathy: a personal history. Circ. Res. 108, 743-750. (doi:10.1161/CIRCRESAHA.110.223834)
7. Ho, C. Y. et al. 2010 Myocardial fibrosis as an early manifestation of hypertrophic cardiomyopathy. N. Engl J. Med. 363, 552-563. (doi:10.1056/ NEJMoa1002659)
8. Tardiff, J. C. 2011 Thin filament mutations: developing an integrative approach to a complex disorder. Circ. Res. 108, 765-782. (doi:10.1161/ CIRCRESAHA.110.224170)
9. Landesberg, A. & Sideman, S. 1994 Mechanical regulation of cardiac muscle by coupling calcium kinetics with cross-bridge cycling: a dynamic model. Am. J. Physiol. 267, H779-H795.
10. Crilley, J. G. et al. 2003 Hypertrophic cardiomyopathy due to sarcomeric gene mutations is characterized by impaired energy metabolism irrespective of the degree of hypertrophy. J. Am. Coll. Cardiol. 41, 1776-1782. (doi:10.1016/S0735-1097(02)03009-7)
11. Harris, S. P., Lyons, R. G. & Bezold, K. L. 2011 In the thick of it: HCM-causing mutations in myosin binding proteins of the thick filament. Circ. Res. 108, 751-764. (doi:10.1161/CIRCRESAHA.110.231670)
12. Beqqali, A., Van Eldik, W., Mummery, C. & Passier, R. 2009 Human stem cells as a model for cardiac differentiation and disease. Cell. Mol. Life Sci. 66, 800-813. (doi:10.1007/s00018-009-8476-0)
13. Gordon, A. M., Homsher, E. & Regnier, M. 2000 Regulation of contraction in striated muscle. Physiol. Rev. 80, 853-924. (Pubitemid 30164950)
14. Spudich, J. A. 2001 The myosin swinging cross-bridge model. Nat. Rev. Mol. Cell Biol. 2, 387-392. (doi:10.1038/35073086)
15. Greenberg, M. J., Watt, J. D., Jones, M., Kazmierczak, K., Szczesna-Cordary, D. & Moore, J. R. 2009 Regulatory light chain mutations associated with cardiomyopathy affect myosin mechanics and kinetics. J. Mol. Cell. Cardiol. 46, 108-115. (doi:10.1016/j.yjmcc.2008.09.126)
16. Tsoutsman, T. et al. 2008 Severe heart failure and early mortality in a double-mutation mouse model of familial hypertrophic cardiomyopathy. Circulation 117, 1820-1831. (doi:10.1161/CIRCULATIONAHA.107.755777)
17. Bai, F., Weis, A., Takeda, A. K., Chase, P. B. & Kawai, M. 2011 Enhanced active cross-bridges during diastole: molecular pathogenesis of tropomyosin's HCMmutations. Biophys. J. 100, 1014-1023. (doi:10.1016/j.bpj.2011. 01.001)
18. Robinson, P., Griffiths, P. J., Watkins, H. & Redwood, C. S. 2007 Dilated and hypertrophic cardiomyopathy mutations in troponin and alpha-tropomyosin have opposing effects on the calcium affinity of cardiac thin filaments. Circ. Res. 101, 1266-1273. (doi:10.1161/CIRCRESAHA.107.156380)
19. Ertz-Berger, B. R., He, H., Dowell, C., Factor, S. M., Haim, T. E., Nunez, S., Schwartz, S. D., Ingwall, J. S. & Tardiff, J. C. 2005 Changes in the chemical and dynamic properties of cardiac troponin T cause discrete cardiomyopathies in transgenic mice. Proc. Natl Acad. Sci. USA 102, 18 219-18 224. (doi:10.1073/pnas.0509181102)
20. Lorenz, M. & Holmes, K. C. 2010 The actin-myosin interface. Proc. Natl Acad. Sci. USA 107, 12 529-12 534. (doi:10.1073/pnas.1003604107)
21. Niederer, S. A., Hunter, P. J. & Smith, N. P. 2006 A quantitative analysis of cardiac myocyte relaxation: a simulation study. Biophys. J. 90, 1697-1722. (doi:10.1529/biophysj.105.069534)
22. Rice, J. J., Wang, F., Bers, D. M. & Tombe, P. P. D. 2008 Approximate model of cooperative activation and cross-bridge cycling in cardiac muscle using ordinary differential equations. Biophys. J. 95, 2368-2390. (doi:10.1529/biophysj.107.119487)
23. Campbell, S. G., Lionetti, F. V., Campbell, K. S. & Mcculloch, A. D. 2010 Coupling of adjacent tropomyosins enhances cross-bridge-mediated cooperative activation in a Markov model of the cardiac thin filament. Biophys. J. 98, 2254-2264. (doi:10.1016/j.bpj.2010.02.010)
24. Bremel, R. D. & Weber, A. 1972 Cooperation within actin filament in vertebrate skeletal muscle. Nat. New Biol. 238, 97-101.
25. Mclachlan, A. D. & Stewart, M. 1975 Tropomyosin coiled-coil interactions: evidence for an unstaggered structure. J. Mol. Biol. 98, 293-304. (doi:10.1016/S0022-2836(75)80119-7)
26. Pan, B. S., Gordon, A. M. & Luo, Z. X. 1989 Removal of tropomyosin overlap modifies cooperative binding of myosin S-1 to reconstituted thin filaments of rabbit striated muscle. J. Biol. Chem. 264, 8495-8498. (Pubitemid 19151560)
27. 2+]i-force relationship in intact twitching cardiac muscle: direct evidence for modulation by isoproterenol and EMD 53998. Biophys. J. 69, 189-201. (doi:10.1016/S0006-3495(95)79889-7)
28. McKillop, D. F. & Geeves, M. A. 1993 Regulation of the interaction between actin and myosin subfragment 1: evidence for three states of the thin filament. Biophys. J. 65, 693-701. (doi:10.1016/S0006-3495(93)81110-X)
29. Rice, J. J., Stolovitzky, G., Tu, Y. & De Tombe, P. P. 2003 Ising model of cardiac thin filament activation with nearest-neighbor cooperative interactions. Biophys. J. 84, 897-909. (doi:10.1016/S0006-3495(03)74907-8)
30. Shiner, J. S. & Solaro, R. J. 1982 Activation of thin-filament- regulated muscle by calcium ion: considerations based on nearest-neighbor lattice statistics. Proc. Natl Acad. Sci. USA 79, 4637-4641. (doi:10.1073/pnas.79.15.4637)
31. Smith, D. A. & Geeves, M. A. 2003 Cooperative regulation of myosin-actin interactions by a continuous flexible chain II: actin-tropomyosin-troponin and regulation by calcium. Biophys. J. 84, 3168-3180. (doi:10.1016/S0006-3495(03)70041-1)
32. Zou, G. & Phillips, G. N. 1994 A cellular automaton model for the regulatory behavior of muscle thin filaments. Biophys. J. 67, 11-28. (doi:10.1016/S0006-3495(94)80475-8)
33. Rice, J. J., Winslow, R. L. & Hunter, W. C. 1999 Comparison of putative cooperative mechanisms in cardiac muscle: length dependence and dynamic responses. Am. J. Physiol. 276, H1734-H1754. (Pubitemid 29246563)
34. Vibert, P., Craig, R. & Lehman, W. 1997 Steric-model for activation of muscle thin filaments. J. Mol. Biol. 266, 8-14. (doi:10.1006/jmbi.1996.0800)
35. Bers, D. M. 2002 Cardiac excitation-contraction coupling. Nature 415, 198-205. (doi:10.1038/415198a)
36. Davis, J. P., Norman, C., Kobayashi, T., Solaro, R. J., Swartz, D. R. & Tikunova, S. B. 2007 Effects of thin and thick filament proteins on calcium binding and exchange with cardiac troponin C. Biophys. J. 92, 3195-3206. (doi:10.1529/biophysj.106.095406)
37. Kobayashi, T. & Solaro, R. J. 2005 Calcium, thin filaments, and the integrative biology of cardiac contractility. Annu. Rev. Physiol. 67, 39-67. (doi:10.1146/annurev.physiol.67.040403.114025)
38. Kohl, P. & Sachs, F. 2001 Mechanoelectric feedback in cardiac cells. Phil. Trans. R. Soc. Lond. A 359, 1173-1185. (doi:10.1098/rsta.2001.0824)
39. Campbell, S., Flaim, S., Leem, C. & Mcculloch, A. 2008 Mechanisms of transmurally-varying myocyte electromechanics in an integrated computational model. Phil. Trans. R. Soc. A 366, 3361-3380. (doi:10.1098/rsta.2008.0088)
40. Niederer, S. A. & Smith, N. P. 2007 A mathematical model of the slow force response to stretch in rat ventricular myocytes. Biophys. J. 92, 4030-4044. (doi:10.1529/biophysj.106.095463)
41. Rice, J., Wang, F., Bers, D. & De Tombe, P. 2008 Approximate model of cooperative activation and cross-bridge cycling in cardiac muscle using ordinary differential equations. Biophys. J. 95, 2368-2390. (doi:10.1529/ biophysj.107.119487)
42. Silva, J. R., Pan, H., Wu, D., Nekouzadeh, A., Decker, K. F., Cui, J., Baker, N. A., Sept, D. & Rudy, Y. 2009 A multiscale model linking ion-channel molecular dynamics and electrostatics to the cardiac action potential. Proc. Natl Acad. Sci. USA 106, 11 102-11 106. (doi:10.1073/pnas. 0904505106)
43. Greenstein, J., Hinch, R. & Winslow, R. 2006 Mechanisms of excitation-contraction coupling in an integrative model of the cardiac ventricular myocyte. Biophys. J. 90, 77-91. (doi:10.1529/biophysj.105.065169)
44. Stelzer, J. E., Norman, H. S., Chen, P. P., Patel, J. R. & Moss, R. L. 2008 Transmural variation in myosin heavy chain isoform expression modulates the timing of myocardial force generation in porcine left ventricle. J. Physiol. (Lond) 586, 5203-5214. (doi:10.1113/jphysiol.2008.160390)
45. Szczesna-Cordary, D., Jones, M., Moore, J. R., Watt, J., Kerrick, W. G. L., Xu, Y., Wang, Y., Wagg, C. & Lopaschuk, G. D. 2007 Myosin regulatory light chain E22K mutation results in decreased cardiac intracellular calcium and force transients. FASEB J. 21, 3974-3985. (doi:10.1096/fj.07-8630com)
46. Wan, X., Bryant, S. M. & Hart, G. 2003 A topographical study of mechanical and electrical properties of single myocytes isolated from normal guinea-pig ventricular muscle. J. Anat. 202, 525-536. (doi:10.1046/j.1469-7580. 2003.00187.x)
47. Bryant, S. M., Shipsey, S. J. & Hart, G. 1999 Normal regional distribution of membrane current density in rat left ventricle is altered in catecholamine-induced hypertrophy. Cardiovasc. Res. 42, 391-401. (doi:10.1016/S0008-6363(99)00033-4)
48. Cordeiro, J., Greene, L., Heilmann, C., Antzelevitch, D. & Antzelevitch, C. 2004 Transmural heterogeneity of calcium activity and mechanical function in the canine left ventricle. Am. J. Physiol. Heart Circ. Physiol. 286, H1471-H1479. (doi:10.1152/ajpheart.00748.2003)
49. Campbell, S. G., Howard, E., Aguado-Sierra, J., Coppola, B. A., Omens, J. H., Mulligan, L. J., Mcculloch, A. D. & Kerckhoffs, R. C. P. 2009 Effect of transmurally heterogeneous myocyte excitation-contraction coupling on canine left ventricular electromechanics. Exp. Physiol. 94, 541-552. (doi:10.1113/expphysiol.2008.044057)
50. Antzelevitch, C., Sicouri, S., Litovsky, S. H., Lukas, A., Krishnan, S. C., Di Diego, J. M., Gintant, G. A. & Liu, D. W. 1991 Heterogeneity within the ventricular wall. Electrophysiology and pharmacology of epicardial, endocardial, and M cells. Circ. Res. 69, 1427-1449.
51. Rosati, B., Grau, F., Rodriguez, S., Li, H., Nerbonne, J. M. & Mckinnon, D. 2003 Concordant expression of KChIP2 mRNA, protein and transient outward current throughout the canine ventricle. J. Physiol. (Lond) 548, 815-822. (doi:10.1113/jphysiol.2002.033704)
52. Kondo, R. P., Dederko, D. A., Teutsch, C., Chrast, J., Catalucci, D., Chien, K. R. & Giles, W. R. 2006 Comparison of contraction and calcium handling between right and left ventricular myocytes from adult mouse heart: a role for repolarization waveform. J. Physiol. 571, 131-146. (doi:10.1113/ jphysiol.2005.101428)
53. Laurita, K. R., Katra, R., Wible, B., Wan, X. & Koo, M. H. 2003 Transmural heterogeneity of calcium handling in canine. Circ. Res. 92, 668-675. (doi:10.1161/01.RES.0000062468.25308.27)
54. Bouvagnet, P., Mairhofer, H., Leger, J. O., Puech, P. & Leger, J. J. 1989 Distribution pattern of alpha and beta myosin in normal and diseased human ventricular myocardium. Basic Res. Cardiol. 84, 91-102. (doi:10.1007/BF01907006)
55. Carnes, C. A., Geisbuhler, T. P. & Reiser, P. J. 2004 Age-dependent changes in contraction and regional myocardial myosin heavy chain isoform expression in rats. J. Appl. Physiol. 97, 446-453. (doi:10.1152/japplphysiol. 00439.2003)
56. Dool, J. S., Mak, A. S., Friberg, P., Wahlander, H., Hawrylechko, A. & Adams, M. A. 1995 Regional myosin heavy chain expression in volume and pressure overload induced cardiac hypertrophy. Acta Physiol. Scand. 155, 396-404. (doi:10.1111/j.1748-1716.1995.tb09989.x)
57. Davis, J. S., Hassanzadeh, S., Winitsky, S., Lin, H., Satorius, C., Vemuri, R., Aletras, A. H., Wen, H. & Epstein, N. D. 2001 The overall pattern of cardiac contraction depends on a spatial gradient of myosin regulatory light chain phosphorylation. Cell 107, 631-641. (doi:10.1016/S0092- 8674(01)00586-4)
58. Hidalgo, C., Wu, Y., Peng, J., Siems, W. F., Campbell, K. B. & Granzier, H. 2006 Effect of diastolic pressure on MLC2v phosphorylation in the rat left ventricle. Arch. Biochem. Biophys. 456, 216-223. (doi:10.1016/j.abb. 2006.06.026)
59. Flaim, S. N., Giles, W. R. & Mcculloch, A. D. 2006 Contributions of sustained INa and IKv43 to transmural heterogeneity of early repolarization and arrhythmogenesis in canine left ventricular myocytes. Am. J. Physiol. Heart Circ. Physiol. 291, H2617-H2629. (doi:10.1152/ajpheart.00350.2006)
60. Kerckhoffs, R. C. P., Bovendeerd, P. H. M., Kotte, J. C. S., Prinzen, F. W., Smits, K. & Arts, T. 2003 Homogeneity of cardiac contraction despite physiological asynchrony of depolarization: a model study. Ann. Biomed. Eng. 31, 536-547. (doi:10.1114/1.1566447)
61. Szczesna, D., Ghosh, D., Li, Q., Gomes, A. V., Guzman, G., Arana, C., Zhi, G., Stull, J. T. & Potter, J. D. 2001 Familial hypertrophic cardiomyopathy mutations in the regulatory light chains of myosin affect their structure, Ca2+ binding, and phosphorylation. J. Biol. Chem. 276, 7086-7092. (doi:10.1074/jbc.M009823200)
62. Rosen, B. D. et al. 2005 Left ventricular concentric remodeling is associated with decreased global and regional systolic function: the Multi-Ethnic Study of Atherosclerosis. Circulation 112, 984-991. (doi:10.1161/CIRCULATIONAHA104.500488)
63. Bauer, M., Cheng, S., Jain, M., Ngoy, S., Theodoropoulos, C., Trujillo, A., Lin, F. C. & Liao, R. 2011 Echocardiographic speckle-tracking-based strain imaging for rapid cardiovascular phenotyping in mice. Circ. Res. 108, 908-916. (doi:10.1161/CIRCRESAHA.110.239574)
64. Chuang, J. S., Zemljic-Harpf, A., Ross, R. S., Frank, L. R., Mcculloch, A. D. & Omens, J. H. 2010 Determination of three-dimensional ventricular strain distributions in gene-targeted mice using tagged MRI. Magn. Reson. Med. 64, 1281-1288. (doi:10.1002/mrm.22547)
65. Strijkers, G. J., Bouts, A., Blankesteijn, W. M., Peeters, T. H. J. M., Vilanova, A., Van Prooijen, M. C., Sanders, H. M. H. F., Heijman, E. & Nicolay, K. 2009 Diffusion tensor imaging of left ventricular remodeling in response to myocardial infarction in the mouse. NMR Biomed. 22, 182-190. (doi:10.1002/nbm.1299)
66. Vetter, F. J. & Mcculloch, A. D. 1998 Three-dimensional analysis of regional cardiac function: a model of rabbit ventricular anatomy. Prog. Biophys. Mol. Biol. 69, 157-183. (doi:10.1016/S0079-6107(98)00006-6)
67. Niederer, S. A. & Smith, N. P. 2008 An improved numerical method for strong coupling of excitation and contraction models in the heart. Prog. Biophys. Mol. Biol. 96, 90-111. (doi:10.1016/j.pbiomolbio.2007.08.001)
68. Whiteley, J. P., Bishop, M. J. & Gavaghan, D. J. 2007 Soft tissue modelling of cardiac fibres for use in coupled mechano-electric simulations. Bull. Math. Biol. 69, 2199-2225. (doi:10.1007/s11538-007-9213-1)
69. Kerckhoffs, R. C. P., Neal, M. L., Gu, Q., Bassingthwaighte, J. B., Omens, J. H. & Mcculloch, A. D. 2007 Coupling of a 3D finite element model of cardiac ventricular mechanics to lumped systems models of the systemic and pulmonic circulation. Ann. Biomed. Eng. 35, 1-18. (doi:10.1007/s10439-006-9212- 7)
70. Kerckhoffs, R. C., Omens, J. H., Mcculloch, A. D. & Mulligan, L. J. 2010 Ventricular dilation and electrical dyssynchrony synergistically increase regional mechanical nonuniformity but not mechanical dyssynchrony: a computational model. Circ. Heart Fail. 3, 528-536. (doi:10.1161/ CIRCHEARTFAILURE.109.862144)
71. Palmer, B. M. et al. 2004 Role of cardiac myosin binding protein C in sustaining left ventricular systolic stiffening. Circ. Res. 94, 1249-1255. (doi:10.1161/01.RES.0000126898.95550.31)
72. Clayton, R. H. et al. 2011 Models of cardiac tissue electrophysiology: progress, challenges and open questions. Prog. Biophys. Mol. Biol. 104, 22-48. (doi:10.1016/j.pbiomolbio.2010.05.008)
73. Cherry, E. M. & Fenton, F. H. 2007 A tale of two dogs: analyzing two models of canine ventricular electrophysiology. Am. J. Physiol. Heart Circ. Physiol. 292, H43-H55. (doi:10.1152/ajpheart.00955.2006)
74. Muthuchamy, M. et al. 1999 Mouse model of a familial hypertrophic cardiomyopathy mutation in alpha-tropomyosin manifests cardiac dysfunction. Circ. Res. 85, 47-56. (Pubitemid 29321041)
75. Scruggs, S. B., Hinken, A. C., Thawornkaiwong, A., Robbins, J., Walker, L. A., De Tombe, P. P., Geenen, D. L., Buttrick, P. M. & Solaro, R. J. 2009 Ablation of ventricular myosin regulatory light chain phosphorylation in mice causes cardiac dysfunction in situ and affects neighboring myofilament protein phosphorylation. J. Biol. Chem. 284, 5097-5106. (doi:10.1074/jbc.M807414200)
76. Varian, K. D. & Janssen, P. M. L. 2007 Frequency-dependent acceleration of relaxation involves decreased myofilament calcium sensitivity. Am. J. Physiol. Heart Circ. Physiol. 292, H2212-H2219. (doi:10.1152/ajpheart. 00778.2006)
77. Ingwall, J. S. 2009 Energy metabolism in heart failure and remodelling. Cardiovasc. Res. 81, 412-419. (doi:10.1093/cvr/cvn301)
78. Cortassa, S., Aon, M. A., O'Rourke, B., Jacques, R., Tseng, H. J., Marban, E. & Winslow, R. L. 2006 A computational model integrating electrophysiology, contraction, and mitochondrial bioenergetics in the ventricular myocyte. Biophys. J. 91, 1564-1589. (doi:10.1529/biophysj.105. 076174)